人bFGF的克隆及其对HeLa细胞生长和血管生成素表达的影响
摘要
宫颈癌是世界女性第二大恶性肿瘤。已经有实验证实血管新生与宫颈癌患者预后不良有关。有多个血管生成因子参与肿瘤血管发生过程,其中主要的有VEGF、bFGF和血管生成素。
bFGF是可以与肝素结合的多功能多肽家族的成员之一。它具有促血管生成的作用,它也在多种肿瘤的增殖和分化中发挥重要作用。研究发现多种恶性肿瘤都高表达bFGF。有学者研究显示宫颈癌患者的血清中bFGF含量增高。血管生成素是唯一一个以促血管发生的功能而命名的血管生成因子。血管生成素在内皮细胞可以发生核转移,进而促进内皮细胞的增殖。血管生成素在HeLa细胞中也有核转移现象,并且能够在细胞核内促进rRNA的合成。
目前对于bFGF和血管生成素的研究主要集中在其如何诱发肿瘤的血管发生,进而促进肿瘤的进一步生长和恶化,以及它们在肿瘤预后评价中的相关作用。而对于二者的关系的研究比较少。有学者发现,应用血管生成素的反义核苷酸可以抑制体外培养的HeLa细胞和体内的肿瘤细胞的生长,但是细胞和肿瘤内的bFGF表达增加。本实验室前期的研究发现,在转染血管生成素反义核苷酸的黑色素瘤细胞中,bFGF的表达增加,而在转染血管生成素正义核苷酸的黑色素瘤细胞中,bFGF的表达降低。为了进一步的研究bFGF与血管生成素的关系,我们克隆了人bFGF基因,并且构建了含有人bFGF基因的正义和反义的真核表达载体,建立了稳定表达bFGF的细胞株。进而探讨在HeLa细胞中,利用bFGF基因的转染改变细胞内源的bFGF基因的表达水平对血管生成素表达的影响。实验结果显示,在转染反义bFGF基因的bFGF低表达细胞株中,细胞表达的bFGF的mRNA和蛋白都降低,细胞的增殖受到了抑制,但是血管生成素的蛋白表达水平却提高了。相反,在转染正义bFGF基因的bFGF高表达的细胞株中,细胞表达的bFGF的mRNA和蛋白均增加,同时细胞的增殖增加,然而血管生成素的的蛋白表达水平下降了。但是,高表达和低表达bFGF的细胞的血管生成素的mRNA水平无显著性差异。对HeLa细胞及高表达bFGF和低表达bFGF的细胞,施加外源的血管生成素后,HeLa细胞和转染反义bFGF基因的低表达bFGF的细胞株,细胞增殖加速,而转染正义bFGF基因的高表达bFGF的细胞株的细胞增殖无改变。实验结果表明,bFGF和血管生成素均可以直接刺激HeLa细胞的增殖。证明外源bFGF基因的转染导致细胞内源bFGF水平发生改变,这一改变负性地影响细胞内源血管生成素蛋白的表达。
Cancer of the uterine cervix is the second most common cancer among women in the world, and the most common gynecological malignancy in P.R. China. Angiogenesis stimulates tumor growth, invasion and metastasis, and therefore is a crucial step in tumorigenesis. Further, evidence of increased neovascularization has been shown to be a negative prognostic indicator in many solid tumors, including cervical cancer. Several growth factors may be involved in the angiogenic process, including angiogenin and basic fibroblast growth factor (bFGF).
Basic fibroblast growth factor (bFGF), a member of a group of heparin-binding multifunctional polypeptides, is one of the most potent angiogenic factors. It is also involved in proliferation and differentiation of a variety of normal and malignant cells and tissues. Many malignant tumors showed an increase in bFGF expression. Angiogenin has been shown to play a role in tumor angiogenesis. Its expression is upregulated in many types of cancers. Angiogenin undergoes nuclear translocation in endothelial cells, which has been shown to be necessary for angiogenesis. Tsuji et al have shown that nuclear translocation of angiogenin occurred in HeLa cells regardless of the cell confluence status, and that angiogenin stimulated rRNA synthesis in HeLa nuclei.
The role of individual angiogenic growth factors in the formation of new blood vessels and in the progression of tumor growth has been extensively investigated. The expression of angiogenin and bFGF is especially associated with a poor prognosis. Nevertheless, little is known about how these factors coordinately regulate tumor angiogenesis and how they react on the targeted inhibition of a single factor. Kishimoto et al have observed that angiogenin antisense HeLa transfectants and tumors in athymic mice actually expressed a higher amount of bFGF than the control
cells and tumors in athymic mice. Song et al demonstrated that the angiogenin sense transfectants actually expressed a lower amount of bFGF, and the angiogenin antisense transfectants expressed a higher amount of bFGF than A375 cells. To further understand the biological role of angiogenin and bFGF, we investigated the influence of bFGF on angiogenin ggene expression and angiogenin secretion in HeLa cell lines.We cloned bFGF and constructed the expression plasmid of bFGF. We transfected the bFGF gene in the sense and ntisense orientation into HeLa cells, and obtained stable bFGF underexpressing and overexpressing transfectants. In our experiments, we demonstrated that inhibition of bFGF gene and protein expression in the bFGF antisense transfectants induced increased protein expression of angiogenin. In contrast, in the bFGF sense transfectants the expression of angiogenin decreased. Delivery of recombinant angiogenin into transfected and control cells led to increased proliferation in the bFGF antisense transfectants and the control cells. However, the cell proliferation had no change in the bFGF sense transfectants. In conclusion, Furthermore, endogenous bFGF affects the expression of angiogenin in HeLa cells.
bFGF是可以与肝素结合的多功能多肽家族的成员之一。它具有促血管生成的作用,它也在多种肿瘤的增殖和分化中发挥重要作用。研究发现多种恶性肿瘤都高表达bFGF。有学者研究显示宫颈癌患者的血清中bFGF含量增高。血管生成素是唯一一个以促血管发生的功能而命名的血管生成因子。血管生成素在内皮细胞可以发生核转移,进而促进内皮细胞的增殖。血管生成素在HeLa细胞中也有核转移现象,并且能够在细胞核内促进rRNA的合成。
目前对于bFGF和血管生成素的研究主要集中在其如何诱发肿瘤的血管发生,进而促进肿瘤的进一步生长和恶化,以及它们在肿瘤预后评价中的相关作用。而对于二者的关系的研究比较少。有学者发现,应用血管生成素的反义核苷酸可以抑制体外培养的HeLa细胞和体内的肿瘤细胞的生长,但是细胞和肿瘤内的bFGF表达增加。本实验室前期的研究发现,在转染血管生成素反义核苷酸的黑色素瘤细胞中,bFGF的表达增加,而在转染血管生成素正义核苷酸的黑色素瘤细胞中,bFGF的表达降低。为了进一步的研究bFGF与血管生成素的关系,我们克隆了人bFGF基因,并且构建了含有人bFGF基因的正义和反义的真核表达载体,建立了稳定表达bFGF的细胞株。进而探讨在HeLa细胞中,利用bFGF基因的转染改变细胞内源的bFGF基因的表达水平对血管生成素表达的影响。实验结果显示,在转染反义bFGF基因的bFGF低表达细胞株中,细胞表达的bFGF的mRNA和蛋白都降低,细胞的增殖受到了抑制,但是血管生成素的蛋白表达水平却提高了。相反,在转染正义bFGF基因的bFGF高表达的细胞株中,细胞表达的bFGF的mRNA和蛋白均增加,同时细胞的增殖增加,然而血管生成素的的蛋白表达水平下降了。但是,高表达和低表达bFGF的细胞的血管生成素的mRNA水平无显著性差异。对HeLa细胞及高表达bFGF和低表达bFGF的细胞,施加外源的血管生成素后,HeLa细胞和转染反义bFGF基因的低表达bFGF的细胞株,细胞增殖加速,而转染正义bFGF基因的高表达bFGF的细胞株的细胞增殖无改变。实验结果表明,bFGF和血管生成素均可以直接刺激HeLa细胞的增殖。证明外源bFGF基因的转染导致细胞内源bFGF水平发生改变,这一改变负性地影响细胞内源血管生成素蛋白的表达。
Cancer of the uterine cervix is the second most common cancer among women in the world, and the most common gynecological malignancy in P.R. China. Angiogenesis stimulates tumor growth, invasion and metastasis, and therefore is a crucial step in tumorigenesis. Further, evidence of increased neovascularization has been shown to be a negative prognostic indicator in many solid tumors, including cervical cancer. Several growth factors may be involved in the angiogenic process, including angiogenin and basic fibroblast growth factor (bFGF).
Basic fibroblast growth factor (bFGF), a member of a group of heparin-binding multifunctional polypeptides, is one of the most potent angiogenic factors. It is also involved in proliferation and differentiation of a variety of normal and malignant cells and tissues. Many malignant tumors showed an increase in bFGF expression. Angiogenin has been shown to play a role in tumor angiogenesis. Its expression is upregulated in many types of cancers. Angiogenin undergoes nuclear translocation in endothelial cells, which has been shown to be necessary for angiogenesis. Tsuji et al have shown that nuclear translocation of angiogenin occurred in HeLa cells regardless of the cell confluence status, and that angiogenin stimulated rRNA synthesis in HeLa nuclei.
The role of individual angiogenic growth factors in the formation of new blood vessels and in the progression of tumor growth has been extensively investigated. The expression of angiogenin and bFGF is especially associated with a poor prognosis. Nevertheless, little is known about how these factors coordinately regulate tumor angiogenesis and how they react on the targeted inhibition of a single factor. Kishimoto et al have observed that angiogenin antisense HeLa transfectants and tumors in athymic mice actually expressed a higher amount of bFGF than the control
cells and tumors in athymic mice. Song et al demonstrated that the angiogenin sense transfectants actually expressed a lower amount of bFGF, and the angiogenin antisense transfectants expressed a higher amount of bFGF than A375 cells. To further understand the biological role of angiogenin and bFGF, we investigated the influence of bFGF on angiogenin ggene expression and angiogenin secretion in HeLa cell lines.We cloned bFGF and constructed the expression plasmid of bFGF. We transfected the bFGF gene in the sense and ntisense orientation into HeLa cells, and obtained stable bFGF underexpressing and overexpressing transfectants. In our experiments, we demonstrated that inhibition of bFGF gene and protein expression in the bFGF antisense transfectants induced increased protein expression of angiogenin. In contrast, in the bFGF sense transfectants the expression of angiogenin decreased. Delivery of recombinant angiogenin into transfected and control cells led to increased proliferation in the bFGF antisense transfectants and the control cells. However, the cell proliferation had no change in the bFGF sense transfectants. In conclusion, Furthermore, endogenous bFGF affects the expression of angiogenin in HeLa cells.
引文
[1]Folkman J. Tumor angiogenesis[C]. In: Holland J F, Frei III E, et al eds. Cancer medicine. 5th ed. Canada: B.C. Decker Inc, 2000. 132–152.
[2]zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application[J]. Nat Rev Cancer, 2002, 2: 342-350.
[3]Ozalp S, Yalcin OT, Oner U, et al. Microvessel density as a prognostic factor in preinvasive and invasive cervical lesions[J]. Eur J Gynaecol Oncol, 2003, 24: 425-428.
[4]Fett JW, Strydom DJ, Lobb RR, et al. Isolation and characterization of angiogenin, an angiogenic protein from human carcinoma cell[J]. Biochemistry, 1985, 24(20): 5480-5486.
[5]Olson KA, Byers HR, Key ME, et al. Prevention of human prostate tumor metastasis in athymic mice by antisense targeting of human angiogenin[J]. Clin Cancer Res, 2001, 7(11): 3598-3605.
[6]Montero S, Guzman C, Cortes-Funes H, et al. Angiogenin expression and prognosis in primary breast carcinoma[J]. Clin Cancer Res, 1998, 4: 2161-2168.
[7]Chopra V, Dinh TV and Hannigan EV. Circulating serum levels of cytokines and angiogenic factors in patients with cervical cancer[J]. Cancer Invest, 1998, 16: 152-159.
[8]Li D, Bell J, Brown A and Berry CL. The observation of angiogenin and basic fibroblast growth factor gene expression in human colonic adenocarcinomas, gastric adenocarcinomas, and hepatocellular carcinomas[J]. J Pathol, 1994, 172: 171-175.
[9]Shimoyama S, Shimizu N, Tsuji E, et al. Distribution of angiogenin and its gene message in colorectal cancer patients and their clinical relevance[J]. Anticancer Res, 2002, 22: 1045-1052.
[10]Chopra V, Dinh TV, et al. Serum levels of interleukins, growth factors and angiogenin in patients with endometrial cancer[J]. J Cancer Res Clin Oncol, 1997, 123: 167-172.
[11]Shimoyama S, Kaminishi M. Increased angiogenin expression in gastric cancer correlated with cancer progression[J]. J Cancer Res Clin Oncol, 2000, (126): 468-474.
[12]Moroianu J, Riordan JF. Nuclear translocation of angiogenin in proliferation endothelial cells is essential to its angiogenic activity[J]. Proc Natl Acad Sci USA, 1994, 91(5): 1677-1681.
[13]Xu ZP, Tsuji T, Riordan JF, et al. The nuclear function of angiogenin in endothelial cells is related to rRNA production[J]. Biochem Biophys Res Commun, 2002, 294: 287-292.
[14]Xu ZP, Tsuji T, Riordan JF, et al. Identificantion and characterization of an angiogenin-binding DNA sequence that stimulates luciferase reporter gene expression[J]. Biochemistry, 2003, 42(1): 121-128.
[15]Tsuji T, Sun Y, Kishimoto K, et al. Angiogenin is translocated to the nucleus of HeLa cells and is involved in ribosomal RNA transcription and cell proliferation[J]. Cancer Res, 2005, 65: 1352-1360.
[16]Basilico C, Moscatelli D. The FGF family of growth factors and oncogenes[J]. Adv. Cancer Res, 1992, 59: 115–165.
[17]Montesano R, Vassalli JD, Baird A, et al. Basic fibroblast growth factor induces angiogenesis in vitro.Proc Natl Acad Sci USA, 1986, 83: 7297-7301.
[18]Gross JL, Herblin WF, Dusak BA, Czerniak P et al. Effects of modulation of basic fibroblast growth factor on tumor growth in vivo[J]. J Natl Cancer Inst, 1993, 85: 121-131.
[19]Fenig E, Wieder R, Paglin S, et al. Basic fibroblast growth factor confers growth inhibition and mitogen-activated protein kinase activation in human breast cancer cells[J]. Clin Cancer Res, 1997, 3: 135-142.
[20]Iwasaki A, Kuwahara M, Yoshinaga Y, et al. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) levels, as prognostic indicators in NSCLC[J]. Eur J Cardiothorac Surg, 2004, 25: 443-448.
[21]Ogasawara S, Yano H, Higaki K, et al. Expression of angiogenic factors, basic fibroblast growth factor and vascular endothelial growth factor, in human biliary tract carcinoma cell lines[J]. Hepatol Res, 2001, 20: 97-113.
[22]Alba E, Llombart A, Ribelles N, et al. Serum endostatin and bFGF as predictive factors in advanced breast cancer patients treated with letrozole[J]. Clin Transl Oncol, 2006, 8: 193-199.
[23]Gravdal K, Halvorsen OJ, Haukaas SA, et al. Expression of bFGF/FGFR-1 and vascular proliferation related to clinicopathologic features and tumor progress in localized prostate cancer[J]. Virchows Arch,2006, 448: 68-74.
[24]Sliutz G, Tempfer C, Obermair A, et al. Serum evaluation of basic fibroblast growth factor in cervical cancer patients[J]. Cancer Lett,1995, 94: 227-231.
[25]Kishimoto K, Liu S, Tsuji T, et al. Endogenous angiogenin in endothelial cells is a general requirement for cell proliferation and angiogenesis[J]. Oncogene, 2005, 4: 445-456.
[26]Song J, Wang J, Yang J, et al. Influence of angiogenin on the growth of A375 human melanoma cells and the expression of basic fibroblast growth factor[J]. Melanoma Res, 2006, 6: 119-126.
[27]Hyder SM, Stancel GM. Regulation of angiogenic growth factors in the female reproductive tract by estrogens and progestins[J]. Mol Endocrinol, 1999, 13: 806–811.
[28]Folkman J. Tumor angiogenesis: therapeutic implications[J]. New Engl J Med, 1971, 285 (7): 1182–1186.
[29]Folkman J. Angiogenesis[C]. In: Braunwald E, Fauci A S, et al eds. Harrison’s text-book of internal medicine. 15th ed. New York: McGraw-Hill, 2001. 517–530.
[30]Baillie CT, Winslet MC, Bradled NJ. Turmor Vasculatur-a potential therapeutic target[J]. Br J Cancer, 1995, 72: 257-267.
[31]Holash J, Maisonpierre PC, Compton D, et al. Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF[J]. Science, 1999, 284(5422):1994–1998.
[32]Folkman J. Tumor angiogenesis[C]. In: Mendelsohn J, Howley P M, Israel M A, Liotta L A, eds. The Molecular Basis of Cancer. Philadelphia: Saunders, 1995. 206–232.
[33]Toi M, Matsumoto T, Bando H. Vascular endothelial growth factor: its prognostic, predictive, and therapeutic implications[J]. Lancet Oncol, 2001, 2(11): 667-673.
[34]Brekken RA, Thorpe PE. Vascular endothelial growth factor and vascular targeting of solid tumors[J]. Anticancer Res, 2001, 21(6B): 4221-4229.
[35]Wellmann S, Taube T, Paal K, et al. Specific reverse transcription-PCR quantification of VEGF splice variants by Lightcyctertechnology[J]. Clin Chem, 2001, 47(4): 654-660.
[36]Petrova TV, Makinen T, Alitalo K. Signaling via vascular endothelial growth factor receptors[J]. Exp Cell Res, 1999, 253(1): 117-130.
[37]Tischer E, Mitchell R, Hartman T, et al. The human gene for vascular endothelial growth factor[J]. J Biol Chem, 1991, 266(18): 11947-11954
[38]陈治,杜钰.血管内皮细胞特异性受体在肿瘤血管靶向治疗中的应用[J].世界华人消化杂志,2001, 9(6): 702– 705.
[39]Wu LW, Mayo LD, Dunbar JD, et al. Utilization of distinct signaling pathways by receptors for vascular endothelial cell growth factor and other mitogens in the induction of endothelial cell proliferation[J]. J Biol Chem, 2000, 275(7): 5096 -5103.
[40]Ferrara N. Vascular endothelial growth factor: molecular and biological aspects[J]. Curr Top Microbiol Immunol, 1999, 237: 1–30.
[41]Kanellis J, Paizis K, Cox AJ, et al. Renal ischemia-reperfusion increases endothelial VEGFR-2 without increasing VEGF or VEGFR-1 expression[J]. Kidney Int, 2002, 61(5): 1696–1706.
[42]Soker S, Takashima S, Miao HQ, et al. Neuropilin-1 is expressed by endothelial and tumor cells as an isoformspecific receptor for vascular endothelial growth factor[J]. Cell, 1998, 92: 735–745.
[43]Gerber HP, McMurtrey A, Kowalski J, et al. VEGF regulates endothelial cell survival throngh the phosphatidylinositol 3’-kinase /Akt signal transduction pathway. Requirement for Flk-1/KDR activation[J]. J Biol Chem, 1998, 273(46): 30336-30343.
[44]Dvorak HF, Brown LF, Detmar M, et al. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis[J]. Am J Path, 1995, 146(5): 1029-1039.
[45]Olofsson B, Jeltsch M, Eriksson U, et al. Current biology of VEGF-B and VEGF-C[J]. Curr Opin Biotechnol, 1999, 10 (6): 528-535.
[46]周泉.血管内皮生长因子的生物学特性及临床研究进展[J].实用心脑肺血管病杂志, 2001, 9(1): 51-54.
[47]毛华,赵敏芳,袁爱力,等.血管内皮生长因子对肝癌细胞侵袭能力和同质性粘附作用影响肿瘤[J], 2002, 22(3): 197-199.
[48]Maglione D, Guerriero V, Viglietto G, et al. Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor[J]. Proc Natl Acad Sci U S A, 1991; 88: 9267–9271.
[49]Viglietto G, Maglione D, Rambaldi M, et al. Upregulation of vascular endothelial growth factor (VEGF) and downregulation of placenta growth factor (PlGF) associated with malignancy in human thyroid tumors and cell lines[J]. Oncogene, 1995, 11: 1569–1579.
[50]Luttun A, Tjwa M, Moons L, et al. Revascularization ofischemic tissues by PlGF treatment, and inhibition oftumor angiogenesis, arthritis and atherosclerosis by anti-Flt-1[J]. Nat Med, 2002, 8: 831–840.
[51]Maglione D, Guerriero V, Viglietto G, et al. Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor[J]. Proc Natl Acad Sci USA, 1991, 88 (20): 9267-9271.
[52]Migdal M, Huppertz B, Tessler S, et al. Neuropilin-1 is a placenta growth factor-2 receptor[J]. J Biol Chem, 1998, 273: 22272–22278.
[53]Hauser S, Weich H. A heparin-binding form of placenta growth factor (PlGF-2) is expressed in human umbilical vein endothelial cells and in placenta[J]. Growth Factors, 1993, 9: 259–68.
[54]Neufeld G, Kessler O, Herzog Y. The interaction of neuropilin-1 and neuropilin-2 with tyrosine-kinase receptors for VEGF[J]. Adv Exp Med Biol, 2002, 515: 81–90.
[55]Park M, Lee ST. The fourth immunoglobulin-like loop in the extracellular domain of Flt-1, a VEGF receptor, includes a major heparinbinding site[J]. Biochem Biophys Res Commun, 1999, 264: 730–734.
[56]Schlessinger J, Plotnikov AN, Ibrahimi OA, et al. Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization[J]. Mol Cell, 2000, 6(3): 743–750.
[57]Soker S, Fidder H, Neufeld G, et al. Characterization of novel vascular endothelial growth factor (VEGF) receptors on tumor cells that bind VEGF165 via its exon 7-encoded domain[J]. J Biol Chem, 1996, 271: 5761–5767.
[58]Errico M, Riccioni T, Iyer S, et al. Identification of placenta growth factor determinants for binding and activation of the flt-1 receptor[J]. J Biol Chem, 2004, 279: 43929–43939.
[59]Lacal PM, Failla CM, Pagani E, et al. Human melanoma cells secrete and respond to placenta growth factor and vascular endothelial growth factor[J]. J Invest Dermatol, 2000, 115: 1000–1007.
[60]Cao Y, O’Reilly MS, Marshall B, et al. Expression ofangiosta tin cDNA in a murine fibrosarcoma suppresses primary tumor growth and produces long-term dormancy of metastases[J]. J Clin Invest, 1998, 101: 1055–1063.
[61]Donnini S, Machein MR, Plate KH, et al. Expression and localization of placenta growth factor and PlGF receptors in human meningiomas[J]. J Pathol, 1999, 189: 66–71.
[62]Wei SC, Tsao PN, Yu SC, et al. Placenta growth factor expression is correlated with survival of patients with colorectal cancer[J]. Gut, 2005, 54: 666–672.
[63]Li B, Sharpe EE, Maupin AB, et al. VEGF and PlGF promote adult vasculogenesis by enhancing EPC recruitment and vessel formation at the site of tumor neovascularization[J]. FASEB J, 2005, 20: 1495–1497.
[64]Takahashi A, Sasaki H, Kim SJ, et al. Identihcation of receptor genes in renal cell carcinoma associated with angiogenesis by differential hybridization technique[J]. Biochem Biophys Res Commun, 1999, 257(3): 855-859.
[65]Matsumoto K, Suzuki K, Koike H, et al. Prognostic significance of plasma placental growth factor levels in renal cell carcinoma association with clinical charact-eristics and vascular endothelial growth factor levels[J]. Anticancer Res, 2003, 23(6D): 4953-4958.
[66]Taylor AP, Osorio L, Craig R, et al. Tumor-specific regulation of anigiogenic growth factor and their rectpors during recovery from cytotoxic therapy[J]. Clin Cancer Res, 2002, 8(4): 1213-1222.
[67]Woo IS, Park MJ, Byun JH, et al. Expression of placental growth factor gene in 1ung cancer[J].Tumor Biol, 2004, 25(122): 1-6.
[68]Lacal PM, Failla CM, Pagani E, et al. Human melanoma cclls secrete and respond to placenta growth factor and vascular endothelial growth factor[J]. J Invest Dermatol, 2000, 115(6): 1000—1007.
[69]Adini A, Kornaga T, Firoozbakht F, et al. Placental growth factor is a suivival factor for tumor endothelial cell and macrophages[J]. Cancer Res, 2002, 62(10): 2749-2752.
[70]Nomura M, Yamagishi S, Harada S, et al. Placenta growth factor (PIGF) mRNA expression in brain tumors[J].J Neurooncol, 1998, 40(2): 123-130.
[71]Heeschen C, Dimmeler S, Fichtlscherer S, et al. Prognostic value of placental growth factor in patients with acute chest pain[J]. JAMA, 2004, 291(4): 435-441.
[72]Burgess WH, Maciag T. The heparin-binding (fibroblast) growth factor family of proteins[J]. Annu Rev Biochem, 1989, 58: 575–606.
[73]Dickson C, Peters G. Potential oncogene product related to growth factors[J]. Nature,1987, 326: 833.
[74]Delli Bovi P, Curatola AM, Kern FG, et al. An oncogene isolated by transfection of Kaposi's sarcoma DNA encodes a growth factor that is a member of the FGF family[J]. Cell, 1987, 50: 729–737.
[75]Yoshida T, Miyagawa K, Odagiri H, et al. Genomic sequence of hst, a transforming gene encoding a protein homologous to fibroblast growth factors and the int-2-encoded protein[J]. Proc Natl Acad Sci U S A, 1987, 84: 7305–7309.
[76]Zhan X, Bates B, Hu XG, et al. The human FGF-5 oncogene encodes a novel protein related to fibroblast growth factors[J]. Mol Cell Biol, 1988, 8(8): 3487–3495.
[77]Coulier F, Ollendorff V, Marics I, et al. The FGF6 gene within the FGF multigene family[J]. Ann. N Y Acad Sci, 1991, 638: 53–61.
[78]Rubin JS, Osada H, Finch PW, et al. Purification and characterization of a newly identified growth factor specific for epithelial cells[J]. Proc Natl Acad Sci U S A, 1989, 86: 802–806.
[79]Tanaka A, Miyamoto K, Minamino N, et al. Cloning and characterization of an androgen-induced growth factor essential for the androgen-dependent growth of mouse mammary carcinoma cells[J]. Proc Natl Acad Sci U S A, 1992, 89: 8928–8932.
[80]Miyamoto M, Naruo K, Seko C, et al. Molecular cloning of a novel cytokine cDNA encoding the ninth member of the fibroblast growth factor family, which has a unique secretion property[J]. Mol Cell Biol, 1993, 13: 4251–4259.
[81]Yamasaki M, Miyake A, Tagashira S, et al. Structure and expression of the rat mRNA encoding a novel member of the fibroblast growth factor family[J]. J Biol Chem, 1996, 271: 15918–15921.
[82]Smallwood PM, Munoz-Sanjuan I, Tong P, et al. Fibroblast growth factor (FGF) homologous factors: new members of the FGF family implicated in nervous system development[J]. Proc Natl Acad Sci U S A, 1996, 93(18): 9850–9857.
[83]McWhirter JR, Goulding M, Weiner JA, et al. A novel fibroblast growth factor gene expressed in the developing nervous system is a downstream target of the chimeric homeodomain oncoprotein E2A-Pbx1[J]. Development, 1997, 124: 3221–3232.
[84]Miyake A, Konishi M, Martin FH, Hernday NA et al. Structure and expression of a novel member, FGF-16, on the fibroblast growth factor family[J]. Biochem Biophys Res Commun, 1998, 243: 148–152.
[85]Hoshikawa M, Ohbayashi N, Yonamine A, et al. Structure and expression of a novel fibroblast growth factor, FGF-17, preferentially expressed in the embryonic brain[J]. Biochem Biophys Res Commun, 1998, 244: 187–191.
[86]Madiai F, Hackshaw KV, Chiu IM. Cloning and characterization of the mouse Fgf-1 gene[J]. Gene, 1996, 179(2): 231–236.
[87]Wang WP, Lehtoma K, Varban ML, et al. Coning of the gene coding for human class 1 heparin-binding growth factor and its expression in fetal tissues[J]. Mol Cell Biol, 1989, 9(6): 2387–2395.
[88]Myers RL, Payson RA, Chotani MA, et al. Gene structure and differential expression of acidic fibroblast growth factor mRNA: identification and distribution of four different transcripts[J]. Oncogene, 1993, 8(2): 341–349.
[89]Crumley G, Dionne CA, Jaye M. The gene for human acidic fibroblast growth factor encodes two upstream exons alternatively spliced to the first coding exon[J]. Biochem Biophys Res Commun, 1990, 171(1): 7–13.
[90]Wang WP, Myers RL, Chiu IM. Single primer-mediated polymerase chain reaction: application in cloning of two different 5'-untranslated sequences of acidic fibroblast growth factor mRNA[J]. DNA Cell Biol, 1991, 10: 771–777.
[91]Chotani MA, Chiu IM. Differential regulation of human fibroblast growth factor 1 transcripts provides a distinct mechanism of cell-specific growth factor expression[J]. Cell Growth Differ, 1997, 8(9): 999–1013.
[92]Myers RL, Chedid M, Tronick SR, et al. Different fibroblast growth factor 1 (FGF-1) transcripts in neural tissues, glioblastomas and kidney carcinoma cell lines[J]. (1995) Oncogene, 1995, 11: 785–789.
[93]Chotani MA, Payson RA, Winkles JA, et al. Human fibroblast growth factor 1 gene expression in vascular smooth muscle cells is modulated via an alternate promoter in response to serum and phorbol ester[J]. Nucleic Acids Res, 1995, 23: 434–441.
[94]Payson RA, Canatan H, Chotani MA, et al. Cloning of two novel forms of human acidic fibroblast growth factor (aFGF) mRNA[J]. Nucleic Acids Res, 1993, 21: 489–495.
[95]Rafferty MA, Fenton JE, Jones AS. An overview of the role and inter-relationship of epidermal growth factor receptor, cyclin D and retinoblastoma protein on the carcinogenesis of squamous cell carcinoma of the larynx[J]. Clin Otolaryngol, 2001, 26(4): 317–320.
[96]Pekny M, Ostman A, Hermansson A, et al. Differences in binding to the solid substratum and extracellular matrix may explain isoform-specific paracrine effects of platelet-derived growth factor[J]. Growth Factors, 1994, 10(2):77–87.
[97]Mehta VB, Connors L, Wang HC, et al. Fibroblast variants nonresponsive to fibroblast growth factor 1 are defective in its nuclear translocation[J]. J Biol Chem, 1998, 273: 4197–4205.
[98]Jackson A, Friedman S, Zhan X, et al. Heat shock induces the release of fibroblast growth factor 1 from NIH 3T3 cells[J]. Proc Natl Acad Sci U S A, 1992, 89(22): 10691–10695.
[99]Chiu IM, Sanberg P and Wang WP. Brain-derived heparin binding growth factors and their oncogenic homologs[C]. In Horrocks LA., Neff NH, Yates AJ, Hadjiconstantinou M. eds. Trophic factors and the Nervous System. New York: Raven Press Ltd, 1990. 57-74.
[100]Chiu IM, Wang WP, Lehtoma K. Alternative splicing generates two forms of mRNA coding for human heparin-binding growth factor 1[J]. Oncogene, 1990, 5(5): 755–762.
[101]Weiner HL, Swain JL. Acidic fibroblast growth factor mRNA is expressed by cardiac myocytes in culture and the protein is localized to the extracellular matrix[J]. Proc Natl Acad Sci U S A, 1989, 86(8): 2683–2687.
[102]Brogi E, Winkles JA, Underwood R, et al. Distinct patterns of expression of fibroblast growth factors and their receptors in human atheroma and nonatherosclerotic arteries. Association of acidic FGF with plaque microvessels and macrophages[J]. J Clin Invest, 1993, 92(50), 2408–2418.
[103]Jaye M, Schlessinger J, Dionne CA. Fibroblast growth factor receptor tyrosine kinases: molecular analysis and signal transduction[J]. Biochim Biophys Acta, 1992, 1135, 185–199.
[104]Aviezer D, Hecht D, Safran M, et al. Perlecan, basal lamina proteoglycan, promotes basic fibroblast growth factor-receptor binding, mitogenesis, and angiogenesis[J]. Cell,1994, 79, 1005–1013.
[105]Burgess WH and Winkles J A. Cell Proliferation in Cancer: Regulatory Mechanisms of Neoplastic Cell Growth[C]. In Pustazi L, Lewis CE, Yap E, eds. United Kingdom: OxfordUniversity Press, 1996. 154–217.
[106]Kan M, Huang JS, Mansson PE, et al. Heparin-binding growth factor type 1 (acidic fibroblast growth factor): a potential biphasic autocrine and paracrine regulator of hepatocyte regeneration[J]. Proc Natl Acad Sci USA, 1989, 86: 7432–7436.
[107]Pirvola U, Cao Y, Oellig C, et al. The site of action of neuronal acidic fibroblast growth factor is the organ of Corti of the rat cochlea[J]. Proc Natl Acad Sci USA, 1995, 92(20): 9269–9273.
[108]Renaud F, Oliver L, Desset S, et al. Up-regulation of aFGF expression in quiescent cells is related to cell survival[J]. J Cell Physiol, 1994, 158(3): 435–443.
[109]Crosby J R, Tappan K A, Seifert R A, et al. Chimera analysis reveals that fibroblasts and endothelial cells require platelet-derived growth factor receptorbeta expression for participation in reactive connective tissue formation in adults but not during development[J]. Am J Pathol, 1999, 154 (5): 1315–1321.
[110]陈纪宁.酸性成纤维生长因子促进引起性骨再生的实验研究[J].中国修复重建外科杂志, 1999, 13(5): 309-314.
[111]陈伟,付小兵,孙同柱,等.胎儿和成人皮肤组织中bFGF、c-fos和c-myc基因转录与翻译的变化及其与创面无瘢愈合的关系[J].中国危重病急救医学, 2002, 14(2): 96-99.
[112]La Rosa S, Uccella S, Erba S, et al. Immunohistochemical detection of fibroblast growth factor receptors in normal endocrine cells and rela ted tumors of the digestive system[J]. Appl Immunohistochem Mol Morphol, 2001, 9(4): 319-328.
[113]Kohler N, Lipton A. Platelets as a source of fibroblast growth-promoting activity[J]. Exp Cell Res, 1974, 87: 297–301.
[114]Ross R, Glomset J, Kariya B, et al. A plateletdependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro[J]. Proc Natl Acad Sci U S A, 1974, 71(4): 1207–1210.
[115]Westermark B, Wasteson A. A platelet factor stimulating human normal glial cells[J]. Exp Cell Res, 1976, 98(1): 170-174.
[116]Johnsson A, Heldin CH, Westermark B, et al. Platelet-derived growth factor: Identification of constituent polypeptide chains[J]. Biochem Biophys Res Commun,1982, 104: 66–74.
[117]Doolittle RF, Hunkapiller MW, Hood LE, et al. Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor[J]. Science, 1983, 221: 275–277.
[118]Waterfield MD, Scrace GT, Whittle N, et al. Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus[J]. Nature, 1983, 304: 35–39.
[119]Betsholtz C, Johnsson A, Heldin CH, et al. cDNA sequence and chromosomal localization of human platelet-derived growth factor A-chain and its expression in tumour cell lines[J]. Nature, 1986, 320: 695–699.
[120]Heldin CH, Johnsson A, Wennergren S, et al A human osteosarcoma cell line secretes a growth factor structurally related to a homodimer of PDGF A-chains[J]. Nature, 1986, 319: 511–514.
[121]Li X, Pontén A, Aase K, et al. PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor[J]. Nat Cell Biol, 2000, 2: 302–309.
[122]Bergsten E, Uutela M, Li X, et al. PDGF-D is a specific, protease-activated ligand for the PDGF beta-receptor[J]. Nat Cell Biol, 2001, 3: 512–516.
[123]LaRochelle WJ, Jeffers M, McDonald WF, et al. PDGF-D, a new protease-activated growth factor[J]. Nat Cell Biol, 2001, 3: 517–521.
[124]Fredriksson L, Li H, Eriksson U. The PDGF family:Four gene products form five dimeric isoforms[J]. Cytokine Growth Factor Rev, 2004, 15: 197–204.
[125]Ekman S, Thuresson ER, Heldin CH, et al. Increased mitogenicity of an alphabeta heterodimeric PDGF receptor complex correlates with lack of RasGAP binding[J]. Oncogene, 1999, 18: 2481–2488.
[126]Stroobant P, Waterfield MD. Purification and properties of porcine platelet-derived growth factor[J]. EMBO J, 1984, 3: 2963–2967.
[127]Hoch RV, Soriano P. Roles of PDGF in animal development[J]. Development, 2003, 130: 4769–4784.
[128]Klinghoffer RA, Hamilton TG, Hoch R, et al. An allelic series at the PDGF_R locus indicates unequal contributions of distinct signaling pathways during development[J]. Dev Cell, 2002, 2: 103–113.
[129]Stiles CD. The molecular biology of platelet derived growth factor[J]. Cell, 1983, 33(3): 653-655.
[130]Su WC, Shiesh SC, Liu HS, et al. Expression of oncongene products HER2/Neu and Ras and fibrosis-related growth factors bFGF and PDGF in bile from biliary malignancies and inflammatory disorders[J]. Dig Dis Sci, 2001, 46(7): 1387-1392.
[131]Feakins RM, Wells CA, Young KA. Platelet-derived growth factor expression in phyllodes tumor and fibroadenomas of the breast[J]. Hum Pathol, 2000, 31 (10): 1214-1222.
[132]Dunn IF, Heese O, Black PM. Growth factors in glioma angiogenesis: FGFs, PDGF, EGF and TGFs[J]. J Neuro oncol, 2000, 50(1-2): 121-137.
[133]Reinmuth N, Liu W, Jung YD, et al. Induction of VEGF in perivascular cells defines a potential paracrine mechanism for endothelial cell survival[J]. FASEB J, 2001, 15 (7): 1239-1241.
[134]Yamaguchi R, Yano H, Iemura A, et al. Expression of vascular endothelial growth factor in human hepato cellulae carcinoma[J]. Hepatology, 1998, 28(1): 68-77.
[135]Bilato C, Pauly RR, Melillo G, et al. Intracellular signaling pathways required for rat vascular smooth muscle cell migration. Interactions between basic fibroblast growth factor and platelet-derived growth factor[J]. J Clin Invest, 1995, 96(4): 1905-1915.
[136]Jiang WG, Martin TA, Parr C, et al. Hepatocyte growth factor, its receptor, and their potential value in cancer therapies[J]. Crit Rev Oncol Hematology, 2005, 53: 35-69.
[137]罗运权,吴孟超.肝细胞生长因子[J].新消化病学杂志, 1997, 5 ( 3) : 198-199.
[138]Nakamura T, Nishizawa T, Hagiya M, et al. Molecular cloning and exp ression of human hepatocyte growth factor[J]. Nature, 1989, 342(6248): 440-443.
[139]Miyazawa K, Tsubouchi H, Naka D, et al. Molecular cloning and sequence analysis of cDNA for human hepatocyte growth factor[J]. Biochem Biophys Res Commun, 1989, 163 (2): 967-973.
[140]Gohda E, Tsubouchi H, Nakayama H, et al. Purification and partial characterization of hepatocyte growth factor from plasma of a patient with fulminant hepatic failure[J]. J Clin Invest, 1988, 81: 414-419.
[141]Bottaro DP, Rubin JS, Faletto DL, et al. Identification of the hepatocyte growth factor recep tor as the c-met proto-oncogene product[J]. Science, 1991, 251(4995): 802-804.
[142]Rosen EM, Nigam SK, Goldberg ID. Scatter factor and the c-met receptor: a paradigmfor mesenchymal/epithelial interaction[J]. J Cell Biol, 1994, 127: 1783 -1787.
[143]Liu Y. Epithelial to mesenchymal transition in renal fibrogenesis: pathologic significance, molecular mechanism, and therapeutic intervention[J]. J Am Soc Nephrol, 2004, 15(1): 1–12.
[144]Matsumoto K, Nakamura T. Hepatocyte growth factor: renotropic role and potential therapeutics for renal diseases[J]. Kidney Int, 2001, 59: 2023–2038.
[145]Rosario M, Birchmeier W. How to make tubes: signaling by the Met receptor tyrosine kinase[J]. Trends Cell Biol, 2003, 13: 328–335.
[146]Vargas GA, Hoeflich A, Jehle PM. Hepatocyte growth factor in renal failure: promise and reality[J]. Kidney Int, 2000, 57: 1426–1436.
[147]Bahary N, Zon LI. Development. Endothelium-2chicken soup for the endoderm[J]. Science, 2001, 294 (5542): 530-531.
[148]Ohmichi H, Koshimizu U, Matsumoto K, et al. Hepatocyte growth factor (HGF) acts as a mesenchyme-derived morphogenic factor during fetal lung development[J]. Development, 1998, 125(7): 1315~1324.
[149]Wislez M, Rabbe N, Marchal J, et al. Hepatocyte growth factor p roduction by neutrophils infiltrating bronchioloalveolar subtype pulmonary adenocarcinoma: role in tumor p rogression and death[J]. Cancer Res, 2003, 63 (6): 1405-1412.
[150]Nicola MH, Bizon R, Machado JJ, et al. Breast cancermicrome tastases: different interactions of carcinoma cellswith normal and cancer patients’bone marrow stromata[J]. Clin Exp Metastasis, 2003, 20(5): 471-479.
[151]Qian CN, Guo X, Cao B, et al. Met p rotein exp ression level correlates with survival in patients with late-stage nasopharyngeal carcinoma[J]. Cancer Res, 2002, 62(2): 589-596.
[152]Xie Q, Liu KD, Hu MY, et al. SF /HGF-c-Met autocrine and paracrine promote metastasis of hepatocellular carcinoma[J]. World J Gastroenterol, 2001, 7 (6): 816-820.
[153]Hasina R, Matsumoto K, Matsumoto-Taniura N, et al. Autocrine and paracrine motility factors and their involvement in invasiveness in a human oral carcinoma cell line[J]. Br J Cancer, 1999, 80 (11): 1708-1717.
[154]Blobe GC, Schiermann WP, Lodish HF. Role of transforming growth factor beta in human disease. N Engl J Med, 2000, 342(18): 1350-1358.
[155]Annes JP, Munger JS, Rifkin DB. Making sense of latent TGF-beta activation[J]. J Cell Sci 2003, 116: 217–224.
[156]Bissell DM, Roulot D, George J. Transforming growth factor beta and the liver[J]. Hepatology, 2001, 34: 859-867.
[157]Meurer SK, Tihaa L, Lahme B, et al. Identification of endoglin in rat hepatic stellate cells: new insights into TGF-βrecep tor signaling[J]. J Bid Chem, 2005, 280: 3078-3087.
[158]Teicher BA.Malignant cells, directors of the malignant process: role of transforming growth factor-beta[J]. Cancer Metasis Rev, 2001, 20: 133-143.
[159]Moustakas A, Stournaras C. Regulation of actin organisation by TGF-beta in H-ras-transformed fibroblasts[J].J Cell Sci, 1999, 12: 1169-1179.
[160]Skinner MK, Parrott JA. Growth factor-mediated cell-cell interactions in the ovary. In: Findly JK, eds. Molecular biology of the female reproductive system. San Diego: Acad Press, 1994, 68-78.
[161]Derynck R. Transforming growth factor-alpha: structure and biological activities[J]. J Cell Biochem, 1986, 32: 203-215.
[162]方友文,许国铭,朱人敏,等.胰腺癌组织表皮生长因子mRNA表达的意义[J].华人消化病杂志, 1998, 6: 256-257.
[163]张静,王文亮,李青,等.α-转化生长因子及其受体在人原发性肝细胞肝癌中的表达意义[J].世界华人消化病杂志, 1999, 7: 939-942.
[164]庄岳鹏,王崇国.肝病患者TGF-α和FGF-β1的表达意义[J].临床肝胆病杂志, 2001, 17: 28-29.
[165]Mendelsohn J. Targeting the epidermal growth factor receptor for cancer therapy[J]. J Clin Oncol, 2002, 20(18 Suppl): 1S-13S.
[166]Ciardiello F, Tortora G. A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor[J]. Clin Cancer Res, 2001, 7(10): 2958-2970.
[167]Hung MC, Lau YK. Basic science of HER-2/neu: a review[J]. Semin Oncol, 1999, 26(4 Supp1): 51-59.
[168]BlumeJensen P, Hunter T. Oncogenic kinase signalling[J]. Nature, 2001, 411(6835): 355-365.
[169]Rosen C J, Pollak M. Circulating IGF-1: New perspectives for a new century[J]. TEM, 1999, 10(4): 136-141.
[170]Shimasaki S, Gao L, Shimonaka M, et al. Isolation and molecular cloning of insulin-like growth factor-binding protein-6[J]. Mol Endocrinol, 1991, 5 :938-948.
[171]Wang HS, Chard T. The role of insulin-like growth factor-I and insulin-like growth factor-binding protein-1 in the control of human fetal growth[J]. J Endocrinol, 1992, 132: 11-19.
[172]Harrington EA, Bennett MR, Fanidi A, et al. c-Myc-induced apoptosis in fibroblasts is inhibited by specific cytokines[J]. EMBO J, 1994, 13(14): 3286-3295
[173]Van Golen CM, Feldman EL. Insulin-like growth factor I is the key growth factor in serum that protects neuroblastoma cells from hyperosmotic-induced apoptosis[J]. J Cell Physiol, 2000, 182: 24-32.
[174]Buerke M, Murohara T, Skurk C, et al. Cardioprotective effect of insulin-like growth factor I in myocardial ischemia followed by reperfusion[J]. Proc Natl Acad Sci USA, 1995, 92(17): 8031-8035.
[175]Müller U, Jongeneel CV, Nedospasov SA, et al. Tumour necrosis factor and lymphotoxin genes map close to H-2D in the mouse major histocompatibility complex[J]. Nature, 1987, 325: 265–267.
[176]Bemelmans MH, van Tits LJ, Buurman WA. Tumor necrosis factor: function, release and clearance[J]. Crit Rev Immunol, 1996, 16: 1–11.
[177]Vandenabeele P, Declercq W, Beyaert R, et al. Two tumour necrosis factor receptors: structure and function[J]. Trends Cell Biol, 1995, 5: 392–399.
[178]Tartaglia LA, Goeddel DV. Two TNF receptors[J]. Immunol Today, 1992, 13: 151–153.
[179]Aggarwal BB. Signalling pathways of the TNF superfamily: a doubleedged sword[J]. Nat Rev Immunol, 2003, 3: 745–756.
[180]刘盂元,史轶蘩.细胞因子在神经内分泌免疫调节网络中的作用[J].国际免疫学杂志, 1993, 6(5): 239-.
[181]杨金升.肿瘤坏死因子在脑卒中时表达及作用[J].国外医学脑血管病分册, 1996, 4(2): 77.
[182]Scavelli C, Vacca A, Di Pietro G, Dammacco F, Ribatti D. Cr-osstalk between angiogenesis and lymphangiogenesis in trmor progression[J]. Leukemia, 2004, 18(3): 1054-1058.
[183]Kassim SK, El-Salahy EM, Fayed ST, et al. Vascular endothelial growth factor and interleukin-8 are associated with poor prognosis in epithelial ovarian cancer patients[J]. Clin Biochem, 2004, 37(5): 363-369.
[184]Nanus DM, Schmitz-Dr?ger BJ, Motzer RJ, et al. Expression of basic fibtoblast growth factor in primary renal tumors corrslation with poor survival[J]. Nat Cancer Inst, 1993, 85: 1597-1598.
[185]Katano M, Nakamura M, Fujimoto K, et al. Prognostic value of platelet-derived growth factor-A (PDGF-A) in gastric carcinoma[J]. Annals surgery, 1998, 227(3): 365-371.
[186]Holley RW, Kiernan JA. "Contact inhibition" of cell division in 3T3 cells[J]. Proc Natl Acad Sci USA, 1968, 60(1): 300-304.
[187]Gospodarowicz D, Moran J. Effect of a fibroblast growth factor, insulin, dexamethasone and serum on the morphology of BALB/c 3T3 cells[J]. Proc Natl Acad Sci USA, 1974, 71 (12): 4648-4652.
[188]CrossMJ, Claesson-Welsh L. FGF and VEGF function in angiogenesis, signaling pathways, biological responses and therapeutic inhibition[J]. Trends Pathways Sci, 2001, 22: 201-201.
[189]Renko M, Quarto N, Morimoto T, et al. Nuclear and cytop -lasmic localiztion of different basic fibtoblast growth factor species[J]. J cell physial, 1990, 144: 108-109.
[190]Patry V, Bugler B, Maret A, et al. Endogenous basic fibroblast growth factor isoforms involved in different intracellular protein complexes[J]. Biochem J, 1997, 326(Pt 1): 259-264.
[191]Ferrara N, Schweigerer L, Neufeld G, et al. Pituitary follicular cells produce basic fibroblast growth factor[J]. Proc Natl Acad Sci USA, 1987, 84(16): 5773-5777.
[192]Eriksson AE, Cousens LS, Weaver LH, et al. Three dimensional structure of human basic fibroblast growth factor[J]. Proc Natl Acad Sci U S A, 1991, 88(8): 3441-3445.
[193]Zhu X, Komiya H, Chirino A, et al. Three-dimensional structure of acidic and basic fibroblast growth factors[J]. Science, 1991 251: 90–93.
[194]Baird A, Schubert D, Ling N, et al. Receptor- and heparin-binding domains of basic fibroblast growth factor[J]. Proc Natl Acad Sci U S A, 1988, 85: 2324–2328.
[195]Thompson SA. The disulfide structure of bovine pituitary basic fibroblast growth factor[J]. J Biol Chem, 1992, 267: 2269–2273.
[196]Sommer AD, Moscatelli D, Rifkin DB. An amino terminally extended and post-translationally modified form of 25 Kd basic fibroblast growth factor[J]. Biochem Biophys Res Commun, 1989 74: 969–976.
[197]Burgess W, Bizik J, Mehlman T, et al. Direct evidence for methylation of arginine residues in high molecular weight forms of basic fibroblast growth factor[J]. Cell Regul, 1991, 2: 87–93.
[198]Quarto N, Finger FP, Rifkin DB. The NH2-terminal extension of high molecular weight bFGF is a nuclear targeting signal[J]. J Cell Physiol, 1991, 147:311–318.
[199]Bugler B, Amalric F, Prats H. Alternative initiation of translation determines cytoplasmic or nuclear localization of basic fibroblast growth factor[J]. Mol Cell Biol, 1991, 11: 573–577.
[200]Patry V, Arnaud E, Amalric F, et al. Involvement of basic fibroblast growth factorNH2 terminus in nuclear retention[J]. Growth Factors, 1995, 11: 163–174.
[201]Basilico C, Moscatelli D. The FGF family of growth factors and oncogenes[J]. Adv Cancer Res, 1992, 59: 115–165.
[202]Jaye M, Schlessinger J, Dionne C. Fibroblast growth factor receptor for acidic and basic fibroblast growth factors[J]. Biochim Biophys Acta, 1992, 1135: 185–199.
[203]Hou JZ, Kan MK, McKeehan K, et al. Fibroblast growth factor receptors from liver vary in three structural domains[J]. Science, 1991, 251: 665–668.
[204]McKeehan WL, Hou J, Adams P, et al. Heparin-binding fibroblast growth factors and prostate cancer[J]. Adv Exp Med Biol, 1993, 330: 203–213.
[205]Werner S, Duan DSR, De Vries C, et al. Differential splicing in the extracellular region of fibroblast growth factor receptor-1 generates receptor variants with different ligand-binding specificities[J]. Mol Cell Biol, 1992, 12: 82–88.
[206]Dell KR, Williams LT. A novel form of fibroblast growth factor receptor 2. Alternative splicing of the third immunoglobulinlike domain confers ligand binding specificity[J]. J Biol Chem, 1992, 267: 21225–21229.
[207]Wang F, Kan M, Xu J, et al. Ligand specific structural domains in the fibroblast growth factor receptor[J]. J Biol Chem, 1995, 270: 1022–1030.
[208]Avivi A, Yayon A, Givol D. A novel form of fibroblast growth factor receptor-3 using an alternative exon in the immunoglobulin domain-III[J]. FEBS Lett, 1993, 330: 249–252.
[209]Chellaiah AT, McEwen DG, Werner S, et al. Fibroblast growth factor receptor (FGFR)-3, Alternative splicing in immunoglobulin-like domain III creates a receptor highly specific for acidic FGF/FGF-1[J]. J Biol Chem, 1994, 269: 11620–11627.
[210]Gilbert E, Del Gatto F, Champion-Arnaud P, et al. Control of BEK and K-SAM splice sites in alternative splicing of the fibroblast growth factor receptor 2 pre-mRNA[J]. Mol Cell Biol, 1993, 13: 5461–5468.
[211]Zimmer Y, Givol D, Yayon A. Multiple structural elements determine ligand binding of fibroblast growth factor receptors.Evidence that both Ig domain 2 and 3 define receptor specificity[J]. J Biol Chem, 1993, 268: 7899–7903.
[212]Wang F, Kan M, Yan G, et al. Alternately spliced NH2 terminal immunoglobulin-like loop I in the ectodomain of fibroblast growth factor (FGF) receptor 1 lowers affinity for both heparin and FGF-1[J]. J Biol Chem, 1995, 270: 10231–10235.
[213]Byers S, Amaya E, Munro S, et al. Fibroblast growth factor receptors contain a conserved HAV region common to cadherins and influenza strain A hemagglutinins: a role in proteinprotein interactions[J]. Dev Biol, 1992, 152: 411–414.
[214]Williams EJ, Walsh FS, Doherty P. The production of arachidonic acid can account for calcium channel activation in the second messenger pathway underlying neurite outgrowth stimulated by NCAM, N-cadherin and L1[J]. J Neurochem, 1994, 62: 1231–1234.
[215]Burrus LW, Zuber ME, Lueddecke BA, et al. Identification of a cysteine-rich receptor for fibroblast growth factors[J]. Mol Cell Biol, 1992, 12: 5600–5609.
[216]Steegmaier M, Levinovitz A, Isenmann S, et al. The E-selectin-ligand ESL-1 is a variant of a receptor for fibroblast growth factor[J]. Nature, 1994, 373: 615–620.
[217]Schwartz SM, Liaw L. Growth control and morphogenesis in the development and pathology of arteries[J]. J Cardiovasc Pharmacol, 1993, 21[Suppl]: S31–S49.
[218]Bikfalvi A, Han ZC. Angiogenic growth factors are hematopoietic growth factors and vice versa[J]. Leukemia, 1994, 8: 523–529.
[219]Allouche M, Bikfalvi A. The role of fibroblast growth factor-2 in hematopoiesis[J]. Prog Growth Factor Res, 1995, 6: 35–48.
[220]Logan A, Frautschy AS, Baird A. Basic fibroblast growth factor and central nervous system injury[J]. AnnNYAcad Sci USA, 1991, 63: 474–476.
[221]Baird A. Fibroblast growth factors: activities and significance of non-neurotrophin neurotrophic growth factors[J]. Curr Opin Neurobiol, 1994, 4: 78–86.
[222]Unsicker K, Engels S, Hamm C, et al. Molecular control of neural plasticity by the multifunctional growth factor families of the FGFs and TGF-b[J]. Anat Anz, 1992, 174: 405–407.
[223]McAvoy JM, Chamberlain GC, de Longh RV, et al. The role of fibroblast growth factor in eye lens development[J]. Ann NY Acad Sci, 1991, 638: 256–274.
[224]Riley BB, Savage MP, Simandl BK, et al. Retroviral expression of FGF-2 (bFGF) affects patterning in chick limb bud[J]. Development, 1993, 118: 95–104.
[225]Fallon JF, Lopez A, Ros MA, et al. FGF-2: apical ectodermal ridge growth signal for chick limb development[J]. Science, 1994, 264: 104–107.
[226]Pallares J, Rojo F, Iriarte J, et al. Study ofmicrovessel density and the expression of the angiogenic factors VEGF, bFGF and the receptors Flt-1 and FLK-1 in benign, premalignant and malignant prostate tissues[J]. 2006, 21 (8): 857-865.
[227]方剑武,黄思罗, Michel Crepin,等. FGF-2/FGFR,信号转导途径与肿瘤的关系及其在乳腺癌发生中的作用[J].科学通报, 2003, 48(13): 1384-1392.
[228]Abuhaibeid S, Czubayko F, Aiqner A. The fibroblast growth factor - binding p rotein FGF-BP[J]. Int J Biochem CellBiol, 2006, 38(9): 1463-1468.
[229]Strydom DJ, Fett JW, Lobb RR, et al. Amino acid sequence of tumor derived angiogenin[J]. Biochemistry, 1985, 24(20): 5486-5494.
[230]Weremowicz S, Fox EA, Morton CC. Localization of the human angiogenin gene to chromosome band 14q11, proximal to the T cell receptor locus[J]. Am J Hum Genet, 1990, 47(6): 973-981.
[231]Riordan JF. Angiogenin. In Ribonucleases: Structures and Functions. D’Alessio G., and Riordan J F, Eds. New York, NY, Academic Rress, 1997, 459-489.
[232]Kurachi K, Davie EW,Strydom DJ, et al. Sequence of the cDNA and gene for angiogenin, a human angiogenesis factor[J]. Biochemistry, 1985, 24(20): 5494-5499.
[233]Bond MD, Strydom DJ, Vallee BL. Characterization and sequencing of rabbit, pig and mouse Angiogenin: discernment of functionally important resicues and regions[J]. Biochim Biophys Acta, 1993, 1162(1-2): 177-186.
[234]Beintema JJ, Schüller C, Irie M, et al. Molecular evolution of the ribonuclease superfamily[J]. Prog Biophys Mol Biol. 1988; 51(3): 165-192.
[235]Harper JW, Vallee BL. Acovalent angiogenin ribonuclease hybrid with a fourth disulfide bond generated by regional mutagenesis[J]. Biochemistry, 1989, 28(4): 1875-1884.
[236]Hu GF, Chang SI, Riordan JF, et al. An angiogenin-binging protein from endothelial cell[J]. Proc Natl Acad Sci USA, 1991, 88(6): 2227-2231.
[237]Hu GF, Strydom DJ, Fett JW, et al. Actin is a binding protein for angiogenin[J]. Proc Natl Acad Sci USA, 1993, 90(4): 1217-1221.
[238]Olson KA, Fett JW, French TC, et al. Angiogenin antagonists prevent tumor growth in vivo[J]. Proc Natl Acad Sci USA, 1995, 92(2): 442-446.
[239]Adams SA, Subramanian Vasanta. The angiogenesis: An emerging family of ribonuclease related proteins with diver cellular functions[J]. Angiogenesis, 1999, 3(3): 189-199.
[240]Soncin F, Shapiro R, Fett J W. A cell-surface proteoglycan mediates human adenocarcinoma HT-29 cell adhesion to human angiogenin[J]. J Biol Chem, 1994, 269(12): 8999-9005.
[241]Strydom DJ. The angiogenins[J]. CMLS, 1998, 54(8): 811-824.
[242]Hu G, Xu C, Riordan JF. Human angiogenin is rapidly translocated to the nucleus of human umbilical vein endothelial cells and binds to DNA[J]. J Cell Biochem, 2000, 76(3): 452-462.
[243]Li R, Riordan JF, Hu GF. Nuclear translocation of human angiogenin in cultured human umbilical artery endothelial cells is microtubule and lysosome independent[J]. Biochem Biophys Res Commun, 1997, 238(2): 305-312.
[244]Moroianu J, Riordan JF. Identification of the nucleolar targeting signal of human angiogenin[J]. Biochem Biophys Res Commun, 1994, 203(4): 1765-1772.
[245]Riordan JF. Angiogenin[J]. Methods Enzymol, 2001, 341: 263-273.
[246]Li LY, Zhang YZ, Zheng YF, et al. An in vitro nuclear run on assay for nuclear function of angiogenin[J]. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao, 2003, 35(4): 350-354.
[247]Park YW, Kim SM, Min BG, et al. Lymphangioma involving the mandible: immunohistochemical expressions for the lymphatic proliferation[J]. J Oral Pathol Med, 2002, 31(5): 280–283.
[248]Alexandrakis MG, Passam FH, Sfiridaki A, et al. Elevated serum angiogenin in multiple myeloma[J]. Hematol J, 2003, 4(6): 454-455.
[249]Glenjen N, Mosevoll KA, Bruserud O. Serum levels of angiogenin, basic fibroblast growth factor and endostatin in patients receiving intensive chemotherapy for acute mylogenous leukemia[J]. Int J Cancer, 2002, 101(1): 86-94.
[250]Danielsen T, Rofstad EK. VEGF, bFGF and EGF in the angiogenesis of human melanoma xenografts[J]. Int J Cancer, 1998, 76(6): 836-841.
[251]Inoue K, Perrotte P, Wood CG, et al. Gene therapy of human bladder cancer with adenovirus-mediated antisense basic fibroblast growth factor. Clin Cancer Res, 2000, 6(11): 4422～4431.
[252]Huang J, Wu L, Tashiro S, Onodera S, et al. Fibroblast growth factor-2 suppresses oridonin-induced L929 apoptosis through extracellular signal-regulated kinase-dependent and phosphatidylinositol 3-kinase-independent pathway[J]. J Pharmacol Sci, 2006, 102(3): 305-313.
[253]Gross JL, Herblin WF, Eidsvoog K, et al. Tumor growth regulation by modulation of basic fibroblast growth factor . EXS, 1992, 61: 421-427.
[254]Becker D, Lee PL, Rodeck U, et al. Inhibition of the fibroblast growth factor receptor 1 (FGFR-1) gene in human melanocytes and malignant melanomas leads to inhibition of proliferation and signs indicative of differentiation[J]. Oncogene, 1992. 7: 2303-2313.
[255]Olson KA, French TC, Vallee BL, et al. A monoclonal antibody to human angiogenin suppresses tumour growth in athymic mice[J]. Cancer Res, 1994, 54(17): 4576-4579.
[256] Olson KA, Byers HR, Key MR. Inhibition of prostate carcinoma establishment and metastatic growth in mice by an antiagiogenin monoclonal antibody[J]. Int J Cancer, 2002, 98(6): 923-929.
[257]杨辉,张英起,韩苇.人血管生成素—PE40融合蛋白基因的构建、表达及活性研究[J].中国生物化学与分子生物学报, 200016(6):746-750.
[258]Jenkins JL, Kao RY, Shapiro R. Virtual screening to enrich hit lists from high-throughput screening: a case study on small-molecule inhibitors of angiogenin[J]. Proteins, 2003, 50: 81-93.
[259]Westphal JR, Van't Hullenaar R, Peek R, et al. Angiogenic balance in human melanoma: expression of VEGF bFGF, IL-8, PDGF and angiostatin in relation to vascular density ofxenografts in vivo[J]. Int. J. Cancer, 2000, 86: 768-776.
[260]Graham FL, van der Eb AJ. A new technique for the assay of infectivity of human adenovirus 5 DNA[J] . Virology, 1973, 52(2):456-467.
[261]Wigler M, Silverstein S, Lee LS, et al. Transfer of purified herpes virus thymidine kinase gene to cultured mouse cells[J]. Cell, 1977, 11(1): 223-232.
[262]Gehl J. Electroporation: theory and methods, perspectives for drug delivery, gene therapy and research[J]. Acta Physiol Scand, 2003, 177 (4): 437-447.
[263]Yanai H, Kubota Y, Nakada T. Effects of electropermeabilization after the administration of anticancer drugs on transitional cell carcinoma[J]. BJU International, 2002, 89(4): 438 - 442.
[264]李燕雄,陈忠东.宫颈癌SiHa细胞脂质体与电穿孔转染效果比较[J].南华大学学报, 2006, 34(4): 526-529.
[265]Gospodarowicz D. Localisation of a fibroblast growth factor and its effect alone and with hydrocortisone on 3T3 cell growth[J]. Nature, 1974, 249(453): 123-127.
[266]Okada-BanM, Thiery J P, Jouanneau J. FibroblaSt growth Factor-2[J]. Int J Biochem Cell Biol, 2000, 32 (3): 263 - 267.
[267]Takayama H, Ray J, Raymon HK, et al. Basic fibroblast growth factor increases dopam inergic graft survival and function in a rat model of Park inson’s disease[J]. Nat Med, 1995, 1: 53-58.
[268]Sasada R, Kurokawa T, Iwane M, et al. Transformation of Mouse BALB/c 3T3 Cells with Human Basic Fibroblast Growth Factor cDNA[J]. Mol Cell Biol, 1988; 8(2): 588-94.
[269]Valesky M, Spang AJ, Fisher GW, et al. Noninvasive dynamic fluorescence imaging of human melanomas reveals that targeted inhibition of bFGF or FGFR-1 in melanoma cells blocks tumor growth by apoptosis[J]. Mol Med, 2002, 8(2): 103-112.
[270]Kuhn H, K?ff C, Konrad J, et al. Influence of basic fibroblast growth factor on the proliferation of non-small cell lung cancer cell lines[J]. Lung Cancer, 2004, 44: 167-174, 2004.
[271]Kuhn H, Konrad J, Holtz S, et al. Enhanced expression of VEGF following bFGF inhibition in non-small cell lung cancer cell lines[J]. Lung Cancer,2006, 54: 149-153.
[272]Polytarchou C, Gligoris T, Kardamakis D, et al. X-rays affect the expression of genes involved in angiogenesis[J]. Anticancer Res, 2004, 24: 2941-2945.
[273]Fersis N, Smyczek-Gargya B, Armeanu S, et al. Changes in vascular enothelial growth factor (VEGF) after chemoendocrine therapy in breast cancer[J]. Eur J Gynaecol Oncol, 2004, 25: 45-50.
[274]Kuhn H, Br?unlich J, Hammerschmidt S, et al. Candidate genes upregulated in density dependent growth inhibition of lung cancer cells[J]. Int J Oncol,2004, 25: 1481-1487.
[2]zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application[J]. Nat Rev Cancer, 2002, 2: 342-350.
[3]Ozalp S, Yalcin OT, Oner U, et al. Microvessel density as a prognostic factor in preinvasive and invasive cervical lesions[J]. Eur J Gynaecol Oncol, 2003, 24: 425-428.
[4]Fett JW, Strydom DJ, Lobb RR, et al. Isolation and characterization of angiogenin, an angiogenic protein from human carcinoma cell[J]. Biochemistry, 1985, 24(20): 5480-5486.
[5]Olson KA, Byers HR, Key ME, et al. Prevention of human prostate tumor metastasis in athymic mice by antisense targeting of human angiogenin[J]. Clin Cancer Res, 2001, 7(11): 3598-3605.
[6]Montero S, Guzman C, Cortes-Funes H, et al. Angiogenin expression and prognosis in primary breast carcinoma[J]. Clin Cancer Res, 1998, 4: 2161-2168.
[7]Chopra V, Dinh TV and Hannigan EV. Circulating serum levels of cytokines and angiogenic factors in patients with cervical cancer[J]. Cancer Invest, 1998, 16: 152-159.
[8]Li D, Bell J, Brown A and Berry CL. The observation of angiogenin and basic fibroblast growth factor gene expression in human colonic adenocarcinomas, gastric adenocarcinomas, and hepatocellular carcinomas[J]. J Pathol, 1994, 172: 171-175.
[9]Shimoyama S, Shimizu N, Tsuji E, et al. Distribution of angiogenin and its gene message in colorectal cancer patients and their clinical relevance[J]. Anticancer Res, 2002, 22: 1045-1052.
[10]Chopra V, Dinh TV, et al. Serum levels of interleukins, growth factors and angiogenin in patients with endometrial cancer[J]. J Cancer Res Clin Oncol, 1997, 123: 167-172.
[11]Shimoyama S, Kaminishi M. Increased angiogenin expression in gastric cancer correlated with cancer progression[J]. J Cancer Res Clin Oncol, 2000, (126): 468-474.
[12]Moroianu J, Riordan JF. Nuclear translocation of angiogenin in proliferation endothelial cells is essential to its angiogenic activity[J]. Proc Natl Acad Sci USA, 1994, 91(5): 1677-1681.
[13]Xu ZP, Tsuji T, Riordan JF, et al. The nuclear function of angiogenin in endothelial cells is related to rRNA production[J]. Biochem Biophys Res Commun, 2002, 294: 287-292.
[14]Xu ZP, Tsuji T, Riordan JF, et al. Identificantion and characterization of an angiogenin-binding DNA sequence that stimulates luciferase reporter gene expression[J]. Biochemistry, 2003, 42(1): 121-128.
[15]Tsuji T, Sun Y, Kishimoto K, et al. Angiogenin is translocated to the nucleus of HeLa cells and is involved in ribosomal RNA transcription and cell proliferation[J]. Cancer Res, 2005, 65: 1352-1360.
[16]Basilico C, Moscatelli D. The FGF family of growth factors and oncogenes[J]. Adv. Cancer Res, 1992, 59: 115–165.
[17]Montesano R, Vassalli JD, Baird A, et al. Basic fibroblast growth factor induces angiogenesis in vitro.Proc Natl Acad Sci USA, 1986, 83: 7297-7301.
[18]Gross JL, Herblin WF, Dusak BA, Czerniak P et al. Effects of modulation of basic fibroblast growth factor on tumor growth in vivo[J]. J Natl Cancer Inst, 1993, 85: 121-131.
[19]Fenig E, Wieder R, Paglin S, et al. Basic fibroblast growth factor confers growth inhibition and mitogen-activated protein kinase activation in human breast cancer cells[J]. Clin Cancer Res, 1997, 3: 135-142.
[20]Iwasaki A, Kuwahara M, Yoshinaga Y, et al. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) levels, as prognostic indicators in NSCLC[J]. Eur J Cardiothorac Surg, 2004, 25: 443-448.
[21]Ogasawara S, Yano H, Higaki K, et al. Expression of angiogenic factors, basic fibroblast growth factor and vascular endothelial growth factor, in human biliary tract carcinoma cell lines[J]. Hepatol Res, 2001, 20: 97-113.
[22]Alba E, Llombart A, Ribelles N, et al. Serum endostatin and bFGF as predictive factors in advanced breast cancer patients treated with letrozole[J]. Clin Transl Oncol, 2006, 8: 193-199.
[23]Gravdal K, Halvorsen OJ, Haukaas SA, et al. Expression of bFGF/FGFR-1 and vascular proliferation related to clinicopathologic features and tumor progress in localized prostate cancer[J]. Virchows Arch,2006, 448: 68-74.
[24]Sliutz G, Tempfer C, Obermair A, et al. Serum evaluation of basic fibroblast growth factor in cervical cancer patients[J]. Cancer Lett,1995, 94: 227-231.
[25]Kishimoto K, Liu S, Tsuji T, et al. Endogenous angiogenin in endothelial cells is a general requirement for cell proliferation and angiogenesis[J]. Oncogene, 2005, 4: 445-456.
[26]Song J, Wang J, Yang J, et al. Influence of angiogenin on the growth of A375 human melanoma cells and the expression of basic fibroblast growth factor[J]. Melanoma Res, 2006, 6: 119-126.
[27]Hyder SM, Stancel GM. Regulation of angiogenic growth factors in the female reproductive tract by estrogens and progestins[J]. Mol Endocrinol, 1999, 13: 806–811.
[28]Folkman J. Tumor angiogenesis: therapeutic implications[J]. New Engl J Med, 1971, 285 (7): 1182–1186.
[29]Folkman J. Angiogenesis[C]. In: Braunwald E, Fauci A S, et al eds. Harrison’s text-book of internal medicine. 15th ed. New York: McGraw-Hill, 2001. 517–530.
[30]Baillie CT, Winslet MC, Bradled NJ. Turmor Vasculatur-a potential therapeutic target[J]. Br J Cancer, 1995, 72: 257-267.
[31]Holash J, Maisonpierre PC, Compton D, et al. Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF[J]. Science, 1999, 284(5422):1994–1998.
[32]Folkman J. Tumor angiogenesis[C]. In: Mendelsohn J, Howley P M, Israel M A, Liotta L A, eds. The Molecular Basis of Cancer. Philadelphia: Saunders, 1995. 206–232.
[33]Toi M, Matsumoto T, Bando H. Vascular endothelial growth factor: its prognostic, predictive, and therapeutic implications[J]. Lancet Oncol, 2001, 2(11): 667-673.
[34]Brekken RA, Thorpe PE. Vascular endothelial growth factor and vascular targeting of solid tumors[J]. Anticancer Res, 2001, 21(6B): 4221-4229.
[35]Wellmann S, Taube T, Paal K, et al. Specific reverse transcription-PCR quantification of VEGF splice variants by Lightcyctertechnology[J]. Clin Chem, 2001, 47(4): 654-660.
[36]Petrova TV, Makinen T, Alitalo K. Signaling via vascular endothelial growth factor receptors[J]. Exp Cell Res, 1999, 253(1): 117-130.
[37]Tischer E, Mitchell R, Hartman T, et al. The human gene for vascular endothelial growth factor[J]. J Biol Chem, 1991, 266(18): 11947-11954
[38]陈治,杜钰.血管内皮细胞特异性受体在肿瘤血管靶向治疗中的应用[J].世界华人消化杂志,2001, 9(6): 702– 705.
[39]Wu LW, Mayo LD, Dunbar JD, et al. Utilization of distinct signaling pathways by receptors for vascular endothelial cell growth factor and other mitogens in the induction of endothelial cell proliferation[J]. J Biol Chem, 2000, 275(7): 5096 -5103.
[40]Ferrara N. Vascular endothelial growth factor: molecular and biological aspects[J]. Curr Top Microbiol Immunol, 1999, 237: 1–30.
[41]Kanellis J, Paizis K, Cox AJ, et al. Renal ischemia-reperfusion increases endothelial VEGFR-2 without increasing VEGF or VEGFR-1 expression[J]. Kidney Int, 2002, 61(5): 1696–1706.
[42]Soker S, Takashima S, Miao HQ, et al. Neuropilin-1 is expressed by endothelial and tumor cells as an isoformspecific receptor for vascular endothelial growth factor[J]. Cell, 1998, 92: 735–745.
[43]Gerber HP, McMurtrey A, Kowalski J, et al. VEGF regulates endothelial cell survival throngh the phosphatidylinositol 3’-kinase /Akt signal transduction pathway. Requirement for Flk-1/KDR activation[J]. J Biol Chem, 1998, 273(46): 30336-30343.
[44]Dvorak HF, Brown LF, Detmar M, et al. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis[J]. Am J Path, 1995, 146(5): 1029-1039.
[45]Olofsson B, Jeltsch M, Eriksson U, et al. Current biology of VEGF-B and VEGF-C[J]. Curr Opin Biotechnol, 1999, 10 (6): 528-535.
[46]周泉.血管内皮生长因子的生物学特性及临床研究进展[J].实用心脑肺血管病杂志, 2001, 9(1): 51-54.
[47]毛华,赵敏芳,袁爱力,等.血管内皮生长因子对肝癌细胞侵袭能力和同质性粘附作用影响肿瘤[J], 2002, 22(3): 197-199.
[48]Maglione D, Guerriero V, Viglietto G, et al. Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor[J]. Proc Natl Acad Sci U S A, 1991; 88: 9267–9271.
[49]Viglietto G, Maglione D, Rambaldi M, et al. Upregulation of vascular endothelial growth factor (VEGF) and downregulation of placenta growth factor (PlGF) associated with malignancy in human thyroid tumors and cell lines[J]. Oncogene, 1995, 11: 1569–1579.
[50]Luttun A, Tjwa M, Moons L, et al. Revascularization ofischemic tissues by PlGF treatment, and inhibition oftumor angiogenesis, arthritis and atherosclerosis by anti-Flt-1[J]. Nat Med, 2002, 8: 831–840.
[51]Maglione D, Guerriero V, Viglietto G, et al. Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor[J]. Proc Natl Acad Sci USA, 1991, 88 (20): 9267-9271.
[52]Migdal M, Huppertz B, Tessler S, et al. Neuropilin-1 is a placenta growth factor-2 receptor[J]. J Biol Chem, 1998, 273: 22272–22278.
[53]Hauser S, Weich H. A heparin-binding form of placenta growth factor (PlGF-2) is expressed in human umbilical vein endothelial cells and in placenta[J]. Growth Factors, 1993, 9: 259–68.
[54]Neufeld G, Kessler O, Herzog Y. The interaction of neuropilin-1 and neuropilin-2 with tyrosine-kinase receptors for VEGF[J]. Adv Exp Med Biol, 2002, 515: 81–90.
[55]Park M, Lee ST. The fourth immunoglobulin-like loop in the extracellular domain of Flt-1, a VEGF receptor, includes a major heparinbinding site[J]. Biochem Biophys Res Commun, 1999, 264: 730–734.
[56]Schlessinger J, Plotnikov AN, Ibrahimi OA, et al. Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization[J]. Mol Cell, 2000, 6(3): 743–750.
[57]Soker S, Fidder H, Neufeld G, et al. Characterization of novel vascular endothelial growth factor (VEGF) receptors on tumor cells that bind VEGF165 via its exon 7-encoded domain[J]. J Biol Chem, 1996, 271: 5761–5767.
[58]Errico M, Riccioni T, Iyer S, et al. Identification of placenta growth factor determinants for binding and activation of the flt-1 receptor[J]. J Biol Chem, 2004, 279: 43929–43939.
[59]Lacal PM, Failla CM, Pagani E, et al. Human melanoma cells secrete and respond to placenta growth factor and vascular endothelial growth factor[J]. J Invest Dermatol, 2000, 115: 1000–1007.
[60]Cao Y, O’Reilly MS, Marshall B, et al. Expression ofangiosta tin cDNA in a murine fibrosarcoma suppresses primary tumor growth and produces long-term dormancy of metastases[J]. J Clin Invest, 1998, 101: 1055–1063.
[61]Donnini S, Machein MR, Plate KH, et al. Expression and localization of placenta growth factor and PlGF receptors in human meningiomas[J]. J Pathol, 1999, 189: 66–71.
[62]Wei SC, Tsao PN, Yu SC, et al. Placenta growth factor expression is correlated with survival of patients with colorectal cancer[J]. Gut, 2005, 54: 666–672.
[63]Li B, Sharpe EE, Maupin AB, et al. VEGF and PlGF promote adult vasculogenesis by enhancing EPC recruitment and vessel formation at the site of tumor neovascularization[J]. FASEB J, 2005, 20: 1495–1497.
[64]Takahashi A, Sasaki H, Kim SJ, et al. Identihcation of receptor genes in renal cell carcinoma associated with angiogenesis by differential hybridization technique[J]. Biochem Biophys Res Commun, 1999, 257(3): 855-859.
[65]Matsumoto K, Suzuki K, Koike H, et al. Prognostic significance of plasma placental growth factor levels in renal cell carcinoma association with clinical charact-eristics and vascular endothelial growth factor levels[J]. Anticancer Res, 2003, 23(6D): 4953-4958.
[66]Taylor AP, Osorio L, Craig R, et al. Tumor-specific regulation of anigiogenic growth factor and their rectpors during recovery from cytotoxic therapy[J]. Clin Cancer Res, 2002, 8(4): 1213-1222.
[67]Woo IS, Park MJ, Byun JH, et al. Expression of placental growth factor gene in 1ung cancer[J].Tumor Biol, 2004, 25(122): 1-6.
[68]Lacal PM, Failla CM, Pagani E, et al. Human melanoma cclls secrete and respond to placenta growth factor and vascular endothelial growth factor[J]. J Invest Dermatol, 2000, 115(6): 1000—1007.
[69]Adini A, Kornaga T, Firoozbakht F, et al. Placental growth factor is a suivival factor for tumor endothelial cell and macrophages[J]. Cancer Res, 2002, 62(10): 2749-2752.
[70]Nomura M, Yamagishi S, Harada S, et al. Placenta growth factor (PIGF) mRNA expression in brain tumors[J].J Neurooncol, 1998, 40(2): 123-130.
[71]Heeschen C, Dimmeler S, Fichtlscherer S, et al. Prognostic value of placental growth factor in patients with acute chest pain[J]. JAMA, 2004, 291(4): 435-441.
[72]Burgess WH, Maciag T. The heparin-binding (fibroblast) growth factor family of proteins[J]. Annu Rev Biochem, 1989, 58: 575–606.
[73]Dickson C, Peters G. Potential oncogene product related to growth factors[J]. Nature,1987, 326: 833.
[74]Delli Bovi P, Curatola AM, Kern FG, et al. An oncogene isolated by transfection of Kaposi's sarcoma DNA encodes a growth factor that is a member of the FGF family[J]. Cell, 1987, 50: 729–737.
[75]Yoshida T, Miyagawa K, Odagiri H, et al. Genomic sequence of hst, a transforming gene encoding a protein homologous to fibroblast growth factors and the int-2-encoded protein[J]. Proc Natl Acad Sci U S A, 1987, 84: 7305–7309.
[76]Zhan X, Bates B, Hu XG, et al. The human FGF-5 oncogene encodes a novel protein related to fibroblast growth factors[J]. Mol Cell Biol, 1988, 8(8): 3487–3495.
[77]Coulier F, Ollendorff V, Marics I, et al. The FGF6 gene within the FGF multigene family[J]. Ann. N Y Acad Sci, 1991, 638: 53–61.
[78]Rubin JS, Osada H, Finch PW, et al. Purification and characterization of a newly identified growth factor specific for epithelial cells[J]. Proc Natl Acad Sci U S A, 1989, 86: 802–806.
[79]Tanaka A, Miyamoto K, Minamino N, et al. Cloning and characterization of an androgen-induced growth factor essential for the androgen-dependent growth of mouse mammary carcinoma cells[J]. Proc Natl Acad Sci U S A, 1992, 89: 8928–8932.
[80]Miyamoto M, Naruo K, Seko C, et al. Molecular cloning of a novel cytokine cDNA encoding the ninth member of the fibroblast growth factor family, which has a unique secretion property[J]. Mol Cell Biol, 1993, 13: 4251–4259.
[81]Yamasaki M, Miyake A, Tagashira S, et al. Structure and expression of the rat mRNA encoding a novel member of the fibroblast growth factor family[J]. J Biol Chem, 1996, 271: 15918–15921.
[82]Smallwood PM, Munoz-Sanjuan I, Tong P, et al. Fibroblast growth factor (FGF) homologous factors: new members of the FGF family implicated in nervous system development[J]. Proc Natl Acad Sci U S A, 1996, 93(18): 9850–9857.
[83]McWhirter JR, Goulding M, Weiner JA, et al. A novel fibroblast growth factor gene expressed in the developing nervous system is a downstream target of the chimeric homeodomain oncoprotein E2A-Pbx1[J]. Development, 1997, 124: 3221–3232.
[84]Miyake A, Konishi M, Martin FH, Hernday NA et al. Structure and expression of a novel member, FGF-16, on the fibroblast growth factor family[J]. Biochem Biophys Res Commun, 1998, 243: 148–152.
[85]Hoshikawa M, Ohbayashi N, Yonamine A, et al. Structure and expression of a novel fibroblast growth factor, FGF-17, preferentially expressed in the embryonic brain[J]. Biochem Biophys Res Commun, 1998, 244: 187–191.
[86]Madiai F, Hackshaw KV, Chiu IM. Cloning and characterization of the mouse Fgf-1 gene[J]. Gene, 1996, 179(2): 231–236.
[87]Wang WP, Lehtoma K, Varban ML, et al. Coning of the gene coding for human class 1 heparin-binding growth factor and its expression in fetal tissues[J]. Mol Cell Biol, 1989, 9(6): 2387–2395.
[88]Myers RL, Payson RA, Chotani MA, et al. Gene structure and differential expression of acidic fibroblast growth factor mRNA: identification and distribution of four different transcripts[J]. Oncogene, 1993, 8(2): 341–349.
[89]Crumley G, Dionne CA, Jaye M. The gene for human acidic fibroblast growth factor encodes two upstream exons alternatively spliced to the first coding exon[J]. Biochem Biophys Res Commun, 1990, 171(1): 7–13.
[90]Wang WP, Myers RL, Chiu IM. Single primer-mediated polymerase chain reaction: application in cloning of two different 5'-untranslated sequences of acidic fibroblast growth factor mRNA[J]. DNA Cell Biol, 1991, 10: 771–777.
[91]Chotani MA, Chiu IM. Differential regulation of human fibroblast growth factor 1 transcripts provides a distinct mechanism of cell-specific growth factor expression[J]. Cell Growth Differ, 1997, 8(9): 999–1013.
[92]Myers RL, Chedid M, Tronick SR, et al. Different fibroblast growth factor 1 (FGF-1) transcripts in neural tissues, glioblastomas and kidney carcinoma cell lines[J]. (1995) Oncogene, 1995, 11: 785–789.
[93]Chotani MA, Payson RA, Winkles JA, et al. Human fibroblast growth factor 1 gene expression in vascular smooth muscle cells is modulated via an alternate promoter in response to serum and phorbol ester[J]. Nucleic Acids Res, 1995, 23: 434–441.
[94]Payson RA, Canatan H, Chotani MA, et al. Cloning of two novel forms of human acidic fibroblast growth factor (aFGF) mRNA[J]. Nucleic Acids Res, 1993, 21: 489–495.
[95]Rafferty MA, Fenton JE, Jones AS. An overview of the role and inter-relationship of epidermal growth factor receptor, cyclin D and retinoblastoma protein on the carcinogenesis of squamous cell carcinoma of the larynx[J]. Clin Otolaryngol, 2001, 26(4): 317–320.
[96]Pekny M, Ostman A, Hermansson A, et al. Differences in binding to the solid substratum and extracellular matrix may explain isoform-specific paracrine effects of platelet-derived growth factor[J]. Growth Factors, 1994, 10(2):77–87.
[97]Mehta VB, Connors L, Wang HC, et al. Fibroblast variants nonresponsive to fibroblast growth factor 1 are defective in its nuclear translocation[J]. J Biol Chem, 1998, 273: 4197–4205.
[98]Jackson A, Friedman S, Zhan X, et al. Heat shock induces the release of fibroblast growth factor 1 from NIH 3T3 cells[J]. Proc Natl Acad Sci U S A, 1992, 89(22): 10691–10695.
[99]Chiu IM, Sanberg P and Wang WP. Brain-derived heparin binding growth factors and their oncogenic homologs[C]. In Horrocks LA., Neff NH, Yates AJ, Hadjiconstantinou M. eds. Trophic factors and the Nervous System. New York: Raven Press Ltd, 1990. 57-74.
[100]Chiu IM, Wang WP, Lehtoma K. Alternative splicing generates two forms of mRNA coding for human heparin-binding growth factor 1[J]. Oncogene, 1990, 5(5): 755–762.
[101]Weiner HL, Swain JL. Acidic fibroblast growth factor mRNA is expressed by cardiac myocytes in culture and the protein is localized to the extracellular matrix[J]. Proc Natl Acad Sci U S A, 1989, 86(8): 2683–2687.
[102]Brogi E, Winkles JA, Underwood R, et al. Distinct patterns of expression of fibroblast growth factors and their receptors in human atheroma and nonatherosclerotic arteries. Association of acidic FGF with plaque microvessels and macrophages[J]. J Clin Invest, 1993, 92(50), 2408–2418.
[103]Jaye M, Schlessinger J, Dionne CA. Fibroblast growth factor receptor tyrosine kinases: molecular analysis and signal transduction[J]. Biochim Biophys Acta, 1992, 1135, 185–199.
[104]Aviezer D, Hecht D, Safran M, et al. Perlecan, basal lamina proteoglycan, promotes basic fibroblast growth factor-receptor binding, mitogenesis, and angiogenesis[J]. Cell,1994, 79, 1005–1013.
[105]Burgess WH and Winkles J A. Cell Proliferation in Cancer: Regulatory Mechanisms of Neoplastic Cell Growth[C]. In Pustazi L, Lewis CE, Yap E, eds. United Kingdom: OxfordUniversity Press, 1996. 154–217.
[106]Kan M, Huang JS, Mansson PE, et al. Heparin-binding growth factor type 1 (acidic fibroblast growth factor): a potential biphasic autocrine and paracrine regulator of hepatocyte regeneration[J]. Proc Natl Acad Sci USA, 1989, 86: 7432–7436.
[107]Pirvola U, Cao Y, Oellig C, et al. The site of action of neuronal acidic fibroblast growth factor is the organ of Corti of the rat cochlea[J]. Proc Natl Acad Sci USA, 1995, 92(20): 9269–9273.
[108]Renaud F, Oliver L, Desset S, et al. Up-regulation of aFGF expression in quiescent cells is related to cell survival[J]. J Cell Physiol, 1994, 158(3): 435–443.
[109]Crosby J R, Tappan K A, Seifert R A, et al. Chimera analysis reveals that fibroblasts and endothelial cells require platelet-derived growth factor receptorbeta expression for participation in reactive connective tissue formation in adults but not during development[J]. Am J Pathol, 1999, 154 (5): 1315–1321.
[110]陈纪宁.酸性成纤维生长因子促进引起性骨再生的实验研究[J].中国修复重建外科杂志, 1999, 13(5): 309-314.
[111]陈伟,付小兵,孙同柱,等.胎儿和成人皮肤组织中bFGF、c-fos和c-myc基因转录与翻译的变化及其与创面无瘢愈合的关系[J].中国危重病急救医学, 2002, 14(2): 96-99.
[112]La Rosa S, Uccella S, Erba S, et al. Immunohistochemical detection of fibroblast growth factor receptors in normal endocrine cells and rela ted tumors of the digestive system[J]. Appl Immunohistochem Mol Morphol, 2001, 9(4): 319-328.
[113]Kohler N, Lipton A. Platelets as a source of fibroblast growth-promoting activity[J]. Exp Cell Res, 1974, 87: 297–301.
[114]Ross R, Glomset J, Kariya B, et al. A plateletdependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro[J]. Proc Natl Acad Sci U S A, 1974, 71(4): 1207–1210.
[115]Westermark B, Wasteson A. A platelet factor stimulating human normal glial cells[J]. Exp Cell Res, 1976, 98(1): 170-174.
[116]Johnsson A, Heldin CH, Westermark B, et al. Platelet-derived growth factor: Identification of constituent polypeptide chains[J]. Biochem Biophys Res Commun,1982, 104: 66–74.
[117]Doolittle RF, Hunkapiller MW, Hood LE, et al. Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor[J]. Science, 1983, 221: 275–277.
[118]Waterfield MD, Scrace GT, Whittle N, et al. Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus[J]. Nature, 1983, 304: 35–39.
[119]Betsholtz C, Johnsson A, Heldin CH, et al. cDNA sequence and chromosomal localization of human platelet-derived growth factor A-chain and its expression in tumour cell lines[J]. Nature, 1986, 320: 695–699.
[120]Heldin CH, Johnsson A, Wennergren S, et al A human osteosarcoma cell line secretes a growth factor structurally related to a homodimer of PDGF A-chains[J]. Nature, 1986, 319: 511–514.
[121]Li X, Pontén A, Aase K, et al. PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor[J]. Nat Cell Biol, 2000, 2: 302–309.
[122]Bergsten E, Uutela M, Li X, et al. PDGF-D is a specific, protease-activated ligand for the PDGF beta-receptor[J]. Nat Cell Biol, 2001, 3: 512–516.
[123]LaRochelle WJ, Jeffers M, McDonald WF, et al. PDGF-D, a new protease-activated growth factor[J]. Nat Cell Biol, 2001, 3: 517–521.
[124]Fredriksson L, Li H, Eriksson U. The PDGF family:Four gene products form five dimeric isoforms[J]. Cytokine Growth Factor Rev, 2004, 15: 197–204.
[125]Ekman S, Thuresson ER, Heldin CH, et al. Increased mitogenicity of an alphabeta heterodimeric PDGF receptor complex correlates with lack of RasGAP binding[J]. Oncogene, 1999, 18: 2481–2488.
[126]Stroobant P, Waterfield MD. Purification and properties of porcine platelet-derived growth factor[J]. EMBO J, 1984, 3: 2963–2967.
[127]Hoch RV, Soriano P. Roles of PDGF in animal development[J]. Development, 2003, 130: 4769–4784.
[128]Klinghoffer RA, Hamilton TG, Hoch R, et al. An allelic series at the PDGF_R locus indicates unequal contributions of distinct signaling pathways during development[J]. Dev Cell, 2002, 2: 103–113.
[129]Stiles CD. The molecular biology of platelet derived growth factor[J]. Cell, 1983, 33(3): 653-655.
[130]Su WC, Shiesh SC, Liu HS, et al. Expression of oncongene products HER2/Neu and Ras and fibrosis-related growth factors bFGF and PDGF in bile from biliary malignancies and inflammatory disorders[J]. Dig Dis Sci, 2001, 46(7): 1387-1392.
[131]Feakins RM, Wells CA, Young KA. Platelet-derived growth factor expression in phyllodes tumor and fibroadenomas of the breast[J]. Hum Pathol, 2000, 31 (10): 1214-1222.
[132]Dunn IF, Heese O, Black PM. Growth factors in glioma angiogenesis: FGFs, PDGF, EGF and TGFs[J]. J Neuro oncol, 2000, 50(1-2): 121-137.
[133]Reinmuth N, Liu W, Jung YD, et al. Induction of VEGF in perivascular cells defines a potential paracrine mechanism for endothelial cell survival[J]. FASEB J, 2001, 15 (7): 1239-1241.
[134]Yamaguchi R, Yano H, Iemura A, et al. Expression of vascular endothelial growth factor in human hepato cellulae carcinoma[J]. Hepatology, 1998, 28(1): 68-77.
[135]Bilato C, Pauly RR, Melillo G, et al. Intracellular signaling pathways required for rat vascular smooth muscle cell migration. Interactions between basic fibroblast growth factor and platelet-derived growth factor[J]. J Clin Invest, 1995, 96(4): 1905-1915.
[136]Jiang WG, Martin TA, Parr C, et al. Hepatocyte growth factor, its receptor, and their potential value in cancer therapies[J]. Crit Rev Oncol Hematology, 2005, 53: 35-69.
[137]罗运权,吴孟超.肝细胞生长因子[J].新消化病学杂志, 1997, 5 ( 3) : 198-199.
[138]Nakamura T, Nishizawa T, Hagiya M, et al. Molecular cloning and exp ression of human hepatocyte growth factor[J]. Nature, 1989, 342(6248): 440-443.
[139]Miyazawa K, Tsubouchi H, Naka D, et al. Molecular cloning and sequence analysis of cDNA for human hepatocyte growth factor[J]. Biochem Biophys Res Commun, 1989, 163 (2): 967-973.
[140]Gohda E, Tsubouchi H, Nakayama H, et al. Purification and partial characterization of hepatocyte growth factor from plasma of a patient with fulminant hepatic failure[J]. J Clin Invest, 1988, 81: 414-419.
[141]Bottaro DP, Rubin JS, Faletto DL, et al. Identification of the hepatocyte growth factor recep tor as the c-met proto-oncogene product[J]. Science, 1991, 251(4995): 802-804.
[142]Rosen EM, Nigam SK, Goldberg ID. Scatter factor and the c-met receptor: a paradigmfor mesenchymal/epithelial interaction[J]. J Cell Biol, 1994, 127: 1783 -1787.
[143]Liu Y. Epithelial to mesenchymal transition in renal fibrogenesis: pathologic significance, molecular mechanism, and therapeutic intervention[J]. J Am Soc Nephrol, 2004, 15(1): 1–12.
[144]Matsumoto K, Nakamura T. Hepatocyte growth factor: renotropic role and potential therapeutics for renal diseases[J]. Kidney Int, 2001, 59: 2023–2038.
[145]Rosario M, Birchmeier W. How to make tubes: signaling by the Met receptor tyrosine kinase[J]. Trends Cell Biol, 2003, 13: 328–335.
[146]Vargas GA, Hoeflich A, Jehle PM. Hepatocyte growth factor in renal failure: promise and reality[J]. Kidney Int, 2000, 57: 1426–1436.
[147]Bahary N, Zon LI. Development. Endothelium-2chicken soup for the endoderm[J]. Science, 2001, 294 (5542): 530-531.
[148]Ohmichi H, Koshimizu U, Matsumoto K, et al. Hepatocyte growth factor (HGF) acts as a mesenchyme-derived morphogenic factor during fetal lung development[J]. Development, 1998, 125(7): 1315~1324.
[149]Wislez M, Rabbe N, Marchal J, et al. Hepatocyte growth factor p roduction by neutrophils infiltrating bronchioloalveolar subtype pulmonary adenocarcinoma: role in tumor p rogression and death[J]. Cancer Res, 2003, 63 (6): 1405-1412.
[150]Nicola MH, Bizon R, Machado JJ, et al. Breast cancermicrome tastases: different interactions of carcinoma cellswith normal and cancer patients’bone marrow stromata[J]. Clin Exp Metastasis, 2003, 20(5): 471-479.
[151]Qian CN, Guo X, Cao B, et al. Met p rotein exp ression level correlates with survival in patients with late-stage nasopharyngeal carcinoma[J]. Cancer Res, 2002, 62(2): 589-596.
[152]Xie Q, Liu KD, Hu MY, et al. SF /HGF-c-Met autocrine and paracrine promote metastasis of hepatocellular carcinoma[J]. World J Gastroenterol, 2001, 7 (6): 816-820.
[153]Hasina R, Matsumoto K, Matsumoto-Taniura N, et al. Autocrine and paracrine motility factors and their involvement in invasiveness in a human oral carcinoma cell line[J]. Br J Cancer, 1999, 80 (11): 1708-1717.
[154]Blobe GC, Schiermann WP, Lodish HF. Role of transforming growth factor beta in human disease. N Engl J Med, 2000, 342(18): 1350-1358.
[155]Annes JP, Munger JS, Rifkin DB. Making sense of latent TGF-beta activation[J]. J Cell Sci 2003, 116: 217–224.
[156]Bissell DM, Roulot D, George J. Transforming growth factor beta and the liver[J]. Hepatology, 2001, 34: 859-867.
[157]Meurer SK, Tihaa L, Lahme B, et al. Identification of endoglin in rat hepatic stellate cells: new insights into TGF-βrecep tor signaling[J]. J Bid Chem, 2005, 280: 3078-3087.
[158]Teicher BA.Malignant cells, directors of the malignant process: role of transforming growth factor-beta[J]. Cancer Metasis Rev, 2001, 20: 133-143.
[159]Moustakas A, Stournaras C. Regulation of actin organisation by TGF-beta in H-ras-transformed fibroblasts[J].J Cell Sci, 1999, 12: 1169-1179.
[160]Skinner MK, Parrott JA. Growth factor-mediated cell-cell interactions in the ovary. In: Findly JK, eds. Molecular biology of the female reproductive system. San Diego: Acad Press, 1994, 68-78.
[161]Derynck R. Transforming growth factor-alpha: structure and biological activities[J]. J Cell Biochem, 1986, 32: 203-215.
[162]方友文,许国铭,朱人敏,等.胰腺癌组织表皮生长因子mRNA表达的意义[J].华人消化病杂志, 1998, 6: 256-257.
[163]张静,王文亮,李青,等.α-转化生长因子及其受体在人原发性肝细胞肝癌中的表达意义[J].世界华人消化病杂志, 1999, 7: 939-942.
[164]庄岳鹏,王崇国.肝病患者TGF-α和FGF-β1的表达意义[J].临床肝胆病杂志, 2001, 17: 28-29.
[165]Mendelsohn J. Targeting the epidermal growth factor receptor for cancer therapy[J]. J Clin Oncol, 2002, 20(18 Suppl): 1S-13S.
[166]Ciardiello F, Tortora G. A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor[J]. Clin Cancer Res, 2001, 7(10): 2958-2970.
[167]Hung MC, Lau YK. Basic science of HER-2/neu: a review[J]. Semin Oncol, 1999, 26(4 Supp1): 51-59.
[168]BlumeJensen P, Hunter T. Oncogenic kinase signalling[J]. Nature, 2001, 411(6835): 355-365.
[169]Rosen C J, Pollak M. Circulating IGF-1: New perspectives for a new century[J]. TEM, 1999, 10(4): 136-141.
[170]Shimasaki S, Gao L, Shimonaka M, et al. Isolation and molecular cloning of insulin-like growth factor-binding protein-6[J]. Mol Endocrinol, 1991, 5 :938-948.
[171]Wang HS, Chard T. The role of insulin-like growth factor-I and insulin-like growth factor-binding protein-1 in the control of human fetal growth[J]. J Endocrinol, 1992, 132: 11-19.
[172]Harrington EA, Bennett MR, Fanidi A, et al. c-Myc-induced apoptosis in fibroblasts is inhibited by specific cytokines[J]. EMBO J, 1994, 13(14): 3286-3295
[173]Van Golen CM, Feldman EL. Insulin-like growth factor I is the key growth factor in serum that protects neuroblastoma cells from hyperosmotic-induced apoptosis[J]. J Cell Physiol, 2000, 182: 24-32.
[174]Buerke M, Murohara T, Skurk C, et al. Cardioprotective effect of insulin-like growth factor I in myocardial ischemia followed by reperfusion[J]. Proc Natl Acad Sci USA, 1995, 92(17): 8031-8035.
[175]Müller U, Jongeneel CV, Nedospasov SA, et al. Tumour necrosis factor and lymphotoxin genes map close to H-2D in the mouse major histocompatibility complex[J]. Nature, 1987, 325: 265–267.
[176]Bemelmans MH, van Tits LJ, Buurman WA. Tumor necrosis factor: function, release and clearance[J]. Crit Rev Immunol, 1996, 16: 1–11.
[177]Vandenabeele P, Declercq W, Beyaert R, et al. Two tumour necrosis factor receptors: structure and function[J]. Trends Cell Biol, 1995, 5: 392–399.
[178]Tartaglia LA, Goeddel DV. Two TNF receptors[J]. Immunol Today, 1992, 13: 151–153.
[179]Aggarwal BB. Signalling pathways of the TNF superfamily: a doubleedged sword[J]. Nat Rev Immunol, 2003, 3: 745–756.
[180]刘盂元,史轶蘩.细胞因子在神经内分泌免疫调节网络中的作用[J].国际免疫学杂志, 1993, 6(5): 239-.
[181]杨金升.肿瘤坏死因子在脑卒中时表达及作用[J].国外医学脑血管病分册, 1996, 4(2): 77.
[182]Scavelli C, Vacca A, Di Pietro G, Dammacco F, Ribatti D. Cr-osstalk between angiogenesis and lymphangiogenesis in trmor progression[J]. Leukemia, 2004, 18(3): 1054-1058.
[183]Kassim SK, El-Salahy EM, Fayed ST, et al. Vascular endothelial growth factor and interleukin-8 are associated with poor prognosis in epithelial ovarian cancer patients[J]. Clin Biochem, 2004, 37(5): 363-369.
[184]Nanus DM, Schmitz-Dr?ger BJ, Motzer RJ, et al. Expression of basic fibtoblast growth factor in primary renal tumors corrslation with poor survival[J]. Nat Cancer Inst, 1993, 85: 1597-1598.
[185]Katano M, Nakamura M, Fujimoto K, et al. Prognostic value of platelet-derived growth factor-A (PDGF-A) in gastric carcinoma[J]. Annals surgery, 1998, 227(3): 365-371.
[186]Holley RW, Kiernan JA. "Contact inhibition" of cell division in 3T3 cells[J]. Proc Natl Acad Sci USA, 1968, 60(1): 300-304.
[187]Gospodarowicz D, Moran J. Effect of a fibroblast growth factor, insulin, dexamethasone and serum on the morphology of BALB/c 3T3 cells[J]. Proc Natl Acad Sci USA, 1974, 71 (12): 4648-4652.
[188]CrossMJ, Claesson-Welsh L. FGF and VEGF function in angiogenesis, signaling pathways, biological responses and therapeutic inhibition[J]. Trends Pathways Sci, 2001, 22: 201-201.
[189]Renko M, Quarto N, Morimoto T, et al. Nuclear and cytop -lasmic localiztion of different basic fibtoblast growth factor species[J]. J cell physial, 1990, 144: 108-109.
[190]Patry V, Bugler B, Maret A, et al. Endogenous basic fibroblast growth factor isoforms involved in different intracellular protein complexes[J]. Biochem J, 1997, 326(Pt 1): 259-264.
[191]Ferrara N, Schweigerer L, Neufeld G, et al. Pituitary follicular cells produce basic fibroblast growth factor[J]. Proc Natl Acad Sci USA, 1987, 84(16): 5773-5777.
[192]Eriksson AE, Cousens LS, Weaver LH, et al. Three dimensional structure of human basic fibroblast growth factor[J]. Proc Natl Acad Sci U S A, 1991, 88(8): 3441-3445.
[193]Zhu X, Komiya H, Chirino A, et al. Three-dimensional structure of acidic and basic fibroblast growth factors[J]. Science, 1991 251: 90–93.
[194]Baird A, Schubert D, Ling N, et al. Receptor- and heparin-binding domains of basic fibroblast growth factor[J]. Proc Natl Acad Sci U S A, 1988, 85: 2324–2328.
[195]Thompson SA. The disulfide structure of bovine pituitary basic fibroblast growth factor[J]. J Biol Chem, 1992, 267: 2269–2273.
[196]Sommer AD, Moscatelli D, Rifkin DB. An amino terminally extended and post-translationally modified form of 25 Kd basic fibroblast growth factor[J]. Biochem Biophys Res Commun, 1989 74: 969–976.
[197]Burgess W, Bizik J, Mehlman T, et al. Direct evidence for methylation of arginine residues in high molecular weight forms of basic fibroblast growth factor[J]. Cell Regul, 1991, 2: 87–93.
[198]Quarto N, Finger FP, Rifkin DB. The NH2-terminal extension of high molecular weight bFGF is a nuclear targeting signal[J]. J Cell Physiol, 1991, 147:311–318.
[199]Bugler B, Amalric F, Prats H. Alternative initiation of translation determines cytoplasmic or nuclear localization of basic fibroblast growth factor[J]. Mol Cell Biol, 1991, 11: 573–577.
[200]Patry V, Arnaud E, Amalric F, et al. Involvement of basic fibroblast growth factorNH2 terminus in nuclear retention[J]. Growth Factors, 1995, 11: 163–174.
[201]Basilico C, Moscatelli D. The FGF family of growth factors and oncogenes[J]. Adv Cancer Res, 1992, 59: 115–165.
[202]Jaye M, Schlessinger J, Dionne C. Fibroblast growth factor receptor for acidic and basic fibroblast growth factors[J]. Biochim Biophys Acta, 1992, 1135: 185–199.
[203]Hou JZ, Kan MK, McKeehan K, et al. Fibroblast growth factor receptors from liver vary in three structural domains[J]. Science, 1991, 251: 665–668.
[204]McKeehan WL, Hou J, Adams P, et al. Heparin-binding fibroblast growth factors and prostate cancer[J]. Adv Exp Med Biol, 1993, 330: 203–213.
[205]Werner S, Duan DSR, De Vries C, et al. Differential splicing in the extracellular region of fibroblast growth factor receptor-1 generates receptor variants with different ligand-binding specificities[J]. Mol Cell Biol, 1992, 12: 82–88.
[206]Dell KR, Williams LT. A novel form of fibroblast growth factor receptor 2. Alternative splicing of the third immunoglobulinlike domain confers ligand binding specificity[J]. J Biol Chem, 1992, 267: 21225–21229.
[207]Wang F, Kan M, Xu J, et al. Ligand specific structural domains in the fibroblast growth factor receptor[J]. J Biol Chem, 1995, 270: 1022–1030.
[208]Avivi A, Yayon A, Givol D. A novel form of fibroblast growth factor receptor-3 using an alternative exon in the immunoglobulin domain-III[J]. FEBS Lett, 1993, 330: 249–252.
[209]Chellaiah AT, McEwen DG, Werner S, et al. Fibroblast growth factor receptor (FGFR)-3, Alternative splicing in immunoglobulin-like domain III creates a receptor highly specific for acidic FGF/FGF-1[J]. J Biol Chem, 1994, 269: 11620–11627.
[210]Gilbert E, Del Gatto F, Champion-Arnaud P, et al. Control of BEK and K-SAM splice sites in alternative splicing of the fibroblast growth factor receptor 2 pre-mRNA[J]. Mol Cell Biol, 1993, 13: 5461–5468.
[211]Zimmer Y, Givol D, Yayon A. Multiple structural elements determine ligand binding of fibroblast growth factor receptors.Evidence that both Ig domain 2 and 3 define receptor specificity[J]. J Biol Chem, 1993, 268: 7899–7903.
[212]Wang F, Kan M, Yan G, et al. Alternately spliced NH2 terminal immunoglobulin-like loop I in the ectodomain of fibroblast growth factor (FGF) receptor 1 lowers affinity for both heparin and FGF-1[J]. J Biol Chem, 1995, 270: 10231–10235.
[213]Byers S, Amaya E, Munro S, et al. Fibroblast growth factor receptors contain a conserved HAV region common to cadherins and influenza strain A hemagglutinins: a role in proteinprotein interactions[J]. Dev Biol, 1992, 152: 411–414.
[214]Williams EJ, Walsh FS, Doherty P. The production of arachidonic acid can account for calcium channel activation in the second messenger pathway underlying neurite outgrowth stimulated by NCAM, N-cadherin and L1[J]. J Neurochem, 1994, 62: 1231–1234.
[215]Burrus LW, Zuber ME, Lueddecke BA, et al. Identification of a cysteine-rich receptor for fibroblast growth factors[J]. Mol Cell Biol, 1992, 12: 5600–5609.
[216]Steegmaier M, Levinovitz A, Isenmann S, et al. The E-selectin-ligand ESL-1 is a variant of a receptor for fibroblast growth factor[J]. Nature, 1994, 373: 615–620.
[217]Schwartz SM, Liaw L. Growth control and morphogenesis in the development and pathology of arteries[J]. J Cardiovasc Pharmacol, 1993, 21[Suppl]: S31–S49.
[218]Bikfalvi A, Han ZC. Angiogenic growth factors are hematopoietic growth factors and vice versa[J]. Leukemia, 1994, 8: 523–529.
[219]Allouche M, Bikfalvi A. The role of fibroblast growth factor-2 in hematopoiesis[J]. Prog Growth Factor Res, 1995, 6: 35–48.
[220]Logan A, Frautschy AS, Baird A. Basic fibroblast growth factor and central nervous system injury[J]. AnnNYAcad Sci USA, 1991, 63: 474–476.
[221]Baird A. Fibroblast growth factors: activities and significance of non-neurotrophin neurotrophic growth factors[J]. Curr Opin Neurobiol, 1994, 4: 78–86.
[222]Unsicker K, Engels S, Hamm C, et al. Molecular control of neural plasticity by the multifunctional growth factor families of the FGFs and TGF-b[J]. Anat Anz, 1992, 174: 405–407.
[223]McAvoy JM, Chamberlain GC, de Longh RV, et al. The role of fibroblast growth factor in eye lens development[J]. Ann NY Acad Sci, 1991, 638: 256–274.
[224]Riley BB, Savage MP, Simandl BK, et al. Retroviral expression of FGF-2 (bFGF) affects patterning in chick limb bud[J]. Development, 1993, 118: 95–104.
[225]Fallon JF, Lopez A, Ros MA, et al. FGF-2: apical ectodermal ridge growth signal for chick limb development[J]. Science, 1994, 264: 104–107.
[226]Pallares J, Rojo F, Iriarte J, et al. Study ofmicrovessel density and the expression of the angiogenic factors VEGF, bFGF and the receptors Flt-1 and FLK-1 in benign, premalignant and malignant prostate tissues[J]. 2006, 21 (8): 857-865.
[227]方剑武,黄思罗, Michel Crepin,等. FGF-2/FGFR,信号转导途径与肿瘤的关系及其在乳腺癌发生中的作用[J].科学通报, 2003, 48(13): 1384-1392.
[228]Abuhaibeid S, Czubayko F, Aiqner A. The fibroblast growth factor - binding p rotein FGF-BP[J]. Int J Biochem CellBiol, 2006, 38(9): 1463-1468.
[229]Strydom DJ, Fett JW, Lobb RR, et al. Amino acid sequence of tumor derived angiogenin[J]. Biochemistry, 1985, 24(20): 5486-5494.
[230]Weremowicz S, Fox EA, Morton CC. Localization of the human angiogenin gene to chromosome band 14q11, proximal to the T cell receptor locus[J]. Am J Hum Genet, 1990, 47(6): 973-981.
[231]Riordan JF. Angiogenin. In Ribonucleases: Structures and Functions. D’Alessio G., and Riordan J F, Eds. New York, NY, Academic Rress, 1997, 459-489.
[232]Kurachi K, Davie EW,Strydom DJ, et al. Sequence of the cDNA and gene for angiogenin, a human angiogenesis factor[J]. Biochemistry, 1985, 24(20): 5494-5499.
[233]Bond MD, Strydom DJ, Vallee BL. Characterization and sequencing of rabbit, pig and mouse Angiogenin: discernment of functionally important resicues and regions[J]. Biochim Biophys Acta, 1993, 1162(1-2): 177-186.
[234]Beintema JJ, Schüller C, Irie M, et al. Molecular evolution of the ribonuclease superfamily[J]. Prog Biophys Mol Biol. 1988; 51(3): 165-192.
[235]Harper JW, Vallee BL. Acovalent angiogenin ribonuclease hybrid with a fourth disulfide bond generated by regional mutagenesis[J]. Biochemistry, 1989, 28(4): 1875-1884.
[236]Hu GF, Chang SI, Riordan JF, et al. An angiogenin-binging protein from endothelial cell[J]. Proc Natl Acad Sci USA, 1991, 88(6): 2227-2231.
[237]Hu GF, Strydom DJ, Fett JW, et al. Actin is a binding protein for angiogenin[J]. Proc Natl Acad Sci USA, 1993, 90(4): 1217-1221.
[238]Olson KA, Fett JW, French TC, et al. Angiogenin antagonists prevent tumor growth in vivo[J]. Proc Natl Acad Sci USA, 1995, 92(2): 442-446.
[239]Adams SA, Subramanian Vasanta. The angiogenesis: An emerging family of ribonuclease related proteins with diver cellular functions[J]. Angiogenesis, 1999, 3(3): 189-199.
[240]Soncin F, Shapiro R, Fett J W. A cell-surface proteoglycan mediates human adenocarcinoma HT-29 cell adhesion to human angiogenin[J]. J Biol Chem, 1994, 269(12): 8999-9005.
[241]Strydom DJ. The angiogenins[J]. CMLS, 1998, 54(8): 811-824.
[242]Hu G, Xu C, Riordan JF. Human angiogenin is rapidly translocated to the nucleus of human umbilical vein endothelial cells and binds to DNA[J]. J Cell Biochem, 2000, 76(3): 452-462.
[243]Li R, Riordan JF, Hu GF. Nuclear translocation of human angiogenin in cultured human umbilical artery endothelial cells is microtubule and lysosome independent[J]. Biochem Biophys Res Commun, 1997, 238(2): 305-312.
[244]Moroianu J, Riordan JF. Identification of the nucleolar targeting signal of human angiogenin[J]. Biochem Biophys Res Commun, 1994, 203(4): 1765-1772.
[245]Riordan JF. Angiogenin[J]. Methods Enzymol, 2001, 341: 263-273.
[246]Li LY, Zhang YZ, Zheng YF, et al. An in vitro nuclear run on assay for nuclear function of angiogenin[J]. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao, 2003, 35(4): 350-354.
[247]Park YW, Kim SM, Min BG, et al. Lymphangioma involving the mandible: immunohistochemical expressions for the lymphatic proliferation[J]. J Oral Pathol Med, 2002, 31(5): 280–283.
[248]Alexandrakis MG, Passam FH, Sfiridaki A, et al. Elevated serum angiogenin in multiple myeloma[J]. Hematol J, 2003, 4(6): 454-455.
[249]Glenjen N, Mosevoll KA, Bruserud O. Serum levels of angiogenin, basic fibroblast growth factor and endostatin in patients receiving intensive chemotherapy for acute mylogenous leukemia[J]. Int J Cancer, 2002, 101(1): 86-94.
[250]Danielsen T, Rofstad EK. VEGF, bFGF and EGF in the angiogenesis of human melanoma xenografts[J]. Int J Cancer, 1998, 76(6): 836-841.
[251]Inoue K, Perrotte P, Wood CG, et al. Gene therapy of human bladder cancer with adenovirus-mediated antisense basic fibroblast growth factor. Clin Cancer Res, 2000, 6(11): 4422～4431.
[252]Huang J, Wu L, Tashiro S, Onodera S, et al. Fibroblast growth factor-2 suppresses oridonin-induced L929 apoptosis through extracellular signal-regulated kinase-dependent and phosphatidylinositol 3-kinase-independent pathway[J]. J Pharmacol Sci, 2006, 102(3): 305-313.
[253]Gross JL, Herblin WF, Eidsvoog K, et al. Tumor growth regulation by modulation of basic fibroblast growth factor . EXS, 1992, 61: 421-427.
[254]Becker D, Lee PL, Rodeck U, et al. Inhibition of the fibroblast growth factor receptor 1 (FGFR-1) gene in human melanocytes and malignant melanomas leads to inhibition of proliferation and signs indicative of differentiation[J]. Oncogene, 1992. 7: 2303-2313.
[255]Olson KA, French TC, Vallee BL, et al. A monoclonal antibody to human angiogenin suppresses tumour growth in athymic mice[J]. Cancer Res, 1994, 54(17): 4576-4579.
[256] Olson KA, Byers HR, Key MR. Inhibition of prostate carcinoma establishment and metastatic growth in mice by an antiagiogenin monoclonal antibody[J]. Int J Cancer, 2002, 98(6): 923-929.
[257]杨辉,张英起,韩苇.人血管生成素—PE40融合蛋白基因的构建、表达及活性研究[J].中国生物化学与分子生物学报, 200016(6):746-750.
[258]Jenkins JL, Kao RY, Shapiro R. Virtual screening to enrich hit lists from high-throughput screening: a case study on small-molecule inhibitors of angiogenin[J]. Proteins, 2003, 50: 81-93.
[259]Westphal JR, Van't Hullenaar R, Peek R, et al. Angiogenic balance in human melanoma: expression of VEGF bFGF, IL-8, PDGF and angiostatin in relation to vascular density ofxenografts in vivo[J]. Int. J. Cancer, 2000, 86: 768-776.
[260]Graham FL, van der Eb AJ. A new technique for the assay of infectivity of human adenovirus 5 DNA[J] . Virology, 1973, 52(2):456-467.
[261]Wigler M, Silverstein S, Lee LS, et al. Transfer of purified herpes virus thymidine kinase gene to cultured mouse cells[J]. Cell, 1977, 11(1): 223-232.
[262]Gehl J. Electroporation: theory and methods, perspectives for drug delivery, gene therapy and research[J]. Acta Physiol Scand, 2003, 177 (4): 437-447.
[263]Yanai H, Kubota Y, Nakada T. Effects of electropermeabilization after the administration of anticancer drugs on transitional cell carcinoma[J]. BJU International, 2002, 89(4): 438 - 442.
[264]李燕雄,陈忠东.宫颈癌SiHa细胞脂质体与电穿孔转染效果比较[J].南华大学学报, 2006, 34(4): 526-529.
[265]Gospodarowicz D. Localisation of a fibroblast growth factor and its effect alone and with hydrocortisone on 3T3 cell growth[J]. Nature, 1974, 249(453): 123-127.
[266]Okada-BanM, Thiery J P, Jouanneau J. FibroblaSt growth Factor-2[J]. Int J Biochem Cell Biol, 2000, 32 (3): 263 - 267.
[267]Takayama H, Ray J, Raymon HK, et al. Basic fibroblast growth factor increases dopam inergic graft survival and function in a rat model of Park inson’s disease[J]. Nat Med, 1995, 1: 53-58.
[268]Sasada R, Kurokawa T, Iwane M, et al. Transformation of Mouse BALB/c 3T3 Cells with Human Basic Fibroblast Growth Factor cDNA[J]. Mol Cell Biol, 1988; 8(2): 588-94.
[269]Valesky M, Spang AJ, Fisher GW, et al. Noninvasive dynamic fluorescence imaging of human melanomas reveals that targeted inhibition of bFGF or FGFR-1 in melanoma cells blocks tumor growth by apoptosis[J]. Mol Med, 2002, 8(2): 103-112.
[270]Kuhn H, K?ff C, Konrad J, et al. Influence of basic fibroblast growth factor on the proliferation of non-small cell lung cancer cell lines[J]. Lung Cancer, 2004, 44: 167-174, 2004.
[271]Kuhn H, Konrad J, Holtz S, et al. Enhanced expression of VEGF following bFGF inhibition in non-small cell lung cancer cell lines[J]. Lung Cancer,2006, 54: 149-153.
[272]Polytarchou C, Gligoris T, Kardamakis D, et al. X-rays affect the expression of genes involved in angiogenesis[J]. Anticancer Res, 2004, 24: 2941-2945.
[273]Fersis N, Smyczek-Gargya B, Armeanu S, et al. Changes in vascular enothelial growth factor (VEGF) after chemoendocrine therapy in breast cancer[J]. Eur J Gynaecol Oncol, 2004, 25: 45-50.
[274]Kuhn H, Br?unlich J, Hammerschmidt S, et al. Candidate genes upregulated in density dependent growth inhibition of lung cancer cells[J]. Int J Oncol,2004, 25: 1481-1487.