PTEN和IGF-1R在喉鳞癌中的相关研究及临床意义
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摘要
目的本研究应用免疫组化SP的方法检测了喉鳞状细胞癌中PTEN和IGF-1R蛋白的表达情况,并分析它们与喉鳞状细胞癌临床生物学特性的关系,探讨它们与喉鳞状细胞癌中发生、发展的关系,为临床对该病的诊断、治疗估计提供理论参考与帮助。方法取喉部鳞状细胞癌(LSCC)石蜡标本50例作为研究对象,所有病例临床数据完整,术前未经化疗、放疗等,术后经病理确诊为喉鳞癌。另取30例声带息肉(VCP)粘膜标本作为对照组。采用免疫组织化学SP法测定PTEN和IGF-1R的表达,分析PTEN和IGF-1R的表达与喉鳞癌的组织学分化程度、T分级、临床分期及淋巴结转移等的关系。统计学分析应用统计软件SPSS13.0进行分析。P﹥0.05认为差异无统计学意义,P<0.05认为差异有统计学意义,P<0.01认为差异有显著统计学意义。结果PTEN蛋白在喉鳞状细胞癌、声带息肉表达阳性表达率分别为58%和96.7%,两者比较差异有显著统计学意义(P<0.01)。PTEN蛋白在不同病理分级的喉鳞癌中阳性表达率不同,高分化、中分化、低分化阳性表达率分别为75.00%、63.64%、25.00%,三者比较差异有显著统计学意义(P﹤0.01)。在喉鳞状细胞癌患者T分期T1、T2、T3、T4期阳性表达率分别为91.67%、75.00%、30.43%、66.67%,差异有显著统计学意义(P﹤0.01)。在喉鳞状细胞癌患者临床分期I期、II期、III期、IV期阳性表达率为91.67%、80.00%、35.00%、37.50%,差异有显著统计学意义(P﹤0.01)。有淋巴结转移者PTEN蛋白阳性表达率为33.33%,无淋巴结转移者PTEN蛋白阳性表达率为65.79%,两者比较差异有统计学意义(P﹤0.05)。PTEN蛋白在不同年龄,不同性别,不同肿瘤部位差异无统计学意义。随T分期、临床分期的增加、分化程度降低及淋巴结转移,PTEN阳性表达率基本逐渐降低。IGF-1R蛋白在喉鳞状细胞癌、声带息肉表达阳性表达率分别为68.00%和16.70%,两者比较差异有显著统计学意义(P<0.01)。IGF-1R蛋白在不同病理分级的喉鳞癌中阳性表达率不同,高分化、中分化、低分化阳性表达率分别为43.75%、72.73%、91.67%,三者比较差异有显著统计学意义(P﹤0.01)。在喉鳞状细胞癌患者T分期T1、T2、T3、T4期阳性表达率分别为33.33%、58.33%、86.96%、100.00%,差异有统计学意义(P﹤0.05)。在喉鳞状细胞癌患者临床分期I期、II期、III期、IV期阳性表达率为33.33%、50.00%、85.00%、100.00%,差异有显著统计学意义(P﹤0.01)。淋巴结转移者IGF-1R蛋白阳性表达率为100.00%,无淋巴结转移者IGF-1R蛋白阳性表达率为57.89%,两者比较差异显著,P﹤0.01,有统计学意义。IGF-1R蛋白在不同年龄,不同性别,不同肿瘤部位差异无统计学意义。随T分期、临床分期的增加、分化程度降低及淋巴结转移,IGF-1R阳性表达率逐渐增高。PTEN表达阳性的病例中,IGF-1R表达阳性率为51.72%;PTEN表达阴性的病例中,IGF-1R表达阳性率为90.47%。IGF-1R表达阳性的病例中, PTEN表达阳性率为44.11%;IGF-1R表达阴性的病例中, PTEN表达阳性率为87.50%。经Spearman等级相关分析, r= -0.570 ,P=0.000。PTEN表达与IGF-1R表达明显负相关。结论1、喉鳞癌组织中PTEN蛋白表达降低,IGF-1R蛋白表达增高,PTEN缺失和/或蛋白的失活和IGF-1R蛋白的高表达可能在喉鳞癌中起作用。2、PTEN和IGF-1R蛋白表达同喉鳞癌的分化程度、临床分期和淋巴结转移明显相关,PTEN和IGF-1R蛋白表达可能在喉鳞癌的发生发展及侵袭进展中起作用,两者的表达水平可能可作为判断肿瘤恶性程度的标志。推测PTEN缺失和/或失活可能是喉鳞癌的发病机制之一,IGF-1R的过度表达也可能是喉鳞癌的发病机制之一。3、喉鳞癌组织中PTEN蛋白低表达,IGF-1R蛋白高表达,并且呈负相关,推测在喉鳞癌中PTEN与IGF-1R两者之间失衡,并且可能在喉鳞癌中起作用。
Objective This study is to detect the expression of PTEN protein and IGF-1R protein in the Laryngeal squamous cell carcinoma(LSCC)and Polyps of vocal cord (VCP) by S-P Immunohistochemistry methods, and to analyze the relations with LSCC’biology characteristics, and to investigate the relations with occurrence and development of LSCC, so that provide theoretical reference and help to its diagnosis and therapy. Methods To take 50 pieces of petroline samples of Laryngeal squamous cell carcinoma as study object, all cases of disease content of integrity clinical data , preoperative patient were not undergo chemotherapy and/or radiotherapy and so on. After-operative samples were final diagnosis as LSCC by pathological-diagnosis. At the same time, to take 30 pieces of VCP mucosae samples as control group. To detect the expression of PTEN protein and IGF-1R protein in LSCC and VCP by S-P Immunohistochemistry methods, to analyze the relations with histology differentiated degree, T grade, clinical stage and lymph node diversion of LSCC. Statistic analyses were done by SPSS 13.0 software. P﹥0.05 was to consider there are not significant difference statistically. P<0.05 was to consider there are significant difference statistically. P<0.01 was to consider there are notable significant difference statistically. Results The positive rates of PTEN were respectively 58%, 96.7% in LSCC,and VCP, there were notable significant difference between them statistically(P﹤0.01). The positive rates were respectively 75.00%、63.64%、25.00% in well-differentiated, moderately differentiated and poorly differentiated. there were notable significant difference among them statistically(P﹤0.01). The positive rates were respectively 91.67%, 75.00%, 30.43%, 66.67% in T1 grade, T2 grade, T3 grade and T4 grade. There were notable significant difference among them statistically(P﹤0.01).The positive rates were respectively 91.67%、80.00%、35.00%、37.50% in I stage, II stage, III stage and IV stage. There were notable significant difference among them statistically(P﹤0.01).The positive rates were respectively 33.33%, 65.79% in have and without lymph node diversion, there were significant difference between them statistically(P﹤0.05),there are not significant difference statistically among different age, sex, tumour position. With increasing of T grade, clinical stage and lymph node diversion, the positive rates of PTEN were basically gradually cutting down. With cutting down of histology differentiated degree, the positive rates of PTEN were basically gradually cutting down.The positive rates of IGF-1R were respectively 68%, 16.70% in LSCC,and VCP, there were notable significant difference between them statistically (P﹤0.01). The positive rates were respectively 43.75%, 72.73%, 91.67% in well-differentiated, moderately differentiated and poorly differentiated. there were notable significant difference among them statistically (P﹤0.01). The positive rates were respectively 33.33%、58.33%、86.96%、100.00% in T1 grade, T2 grade, T3 grade and T4 grade. There were notable significant difference among them statistically(P﹤0.01), The positive rates were respectively 33.33%、50.00%、85.00%、100.00% in I stage, II stage , III stage and IV stage. there were notable significant difference among them statistically(P﹤0.01).The positive rates were respectively 100%, 57.89% in have and without lymph node diversion, there were notable significant difference between them statistically(P﹤0.01)there are not significant difference statistically among different age, sex, tumour position.With increasing of T grade, clinical stage and lymph node diversion, the positive rates of IGF-1R were basically gradually increasing. With cutting down of histology differentiated degree, the positive rates of IGF-1R were basically gradually increasing. The positive rates of IGF-1R were 51.72% in the cases of PTEN positive expression, the positive rates of IGF-1R were 90.47% in the cases of PTEN negative expression; the positive rates of PTEN were 44.11% in the cases of IGF-1R positive expression, the positive rates of PTEN were 87.50% in the cases IGF-1R of positive expression. Through rank correlation analysis, r= -0.570 ,P=0.000. PTEN expression was obviously negative correlation with IGF-1R expression. Conclusions 1. The expression of PTEN protein is cutting down, the expression of IGF-1R protein is increasing , absence and/or deactivation of PTEN and overexpression of IGF-1R are probably playing a role in LSCC. 2. The expression of PTEN protein and IGF-1R protein are correlated with histology differentiated degree, T grade, clinical stage and lymph node diversion of LSCC. PTEN and IGF-1R probably play a role in occurrence, development, invasion and progress of LSCC, and their expression-level probably become mark to judge tumour’s malignant-degree. We can draw a conclusion that absence and/or deactivation of PTEN and overexpression of IGF-1R are probably section of disease mechanism. 3. The study show that PTEN protein is low-expression, IGF-1R protein is overexpression, and they are negative correlation, so we can infer that there is disequilibrium between PTEN and IGF-1R, and this disequilibrium probably play a role in LSCC.
Objective This study is to detect the expression of PTEN protein and IGF-1R protein in the Laryngeal squamous cell carcinoma(LSCC)and Polyps of vocal cord (VCP) by S-P Immunohistochemistry methods, and to analyze the relations with LSCC’biology characteristics, and to investigate the relations with occurrence and development of LSCC, so that provide theoretical reference and help to its diagnosis and therapy. Methods To take 50 pieces of petroline samples of Laryngeal squamous cell carcinoma as study object, all cases of disease content of integrity clinical data , preoperative patient were not undergo chemotherapy and/or radiotherapy and so on. After-operative samples were final diagnosis as LSCC by pathological-diagnosis. At the same time, to take 30 pieces of VCP mucosae samples as control group. To detect the expression of PTEN protein and IGF-1R protein in LSCC and VCP by S-P Immunohistochemistry methods, to analyze the relations with histology differentiated degree, T grade, clinical stage and lymph node diversion of LSCC. Statistic analyses were done by SPSS 13.0 software. P﹥0.05 was to consider there are not significant difference statistically. P<0.05 was to consider there are significant difference statistically. P<0.01 was to consider there are notable significant difference statistically. Results The positive rates of PTEN were respectively 58%, 96.7% in LSCC,and VCP, there were notable significant difference between them statistically(P﹤0.01). The positive rates were respectively 75.00%、63.64%、25.00% in well-differentiated, moderately differentiated and poorly differentiated. there were notable significant difference among them statistically(P﹤0.01). The positive rates were respectively 91.67%, 75.00%, 30.43%, 66.67% in T1 grade, T2 grade, T3 grade and T4 grade. There were notable significant difference among them statistically(P﹤0.01).The positive rates were respectively 91.67%、80.00%、35.00%、37.50% in I stage, II stage, III stage and IV stage. There were notable significant difference among them statistically(P﹤0.01).The positive rates were respectively 33.33%, 65.79% in have and without lymph node diversion, there were significant difference between them statistically(P﹤0.05),there are not significant difference statistically among different age, sex, tumour position. With increasing of T grade, clinical stage and lymph node diversion, the positive rates of PTEN were basically gradually cutting down. With cutting down of histology differentiated degree, the positive rates of PTEN were basically gradually cutting down.The positive rates of IGF-1R were respectively 68%, 16.70% in LSCC,and VCP, there were notable significant difference between them statistically (P﹤0.01). The positive rates were respectively 43.75%, 72.73%, 91.67% in well-differentiated, moderately differentiated and poorly differentiated. there were notable significant difference among them statistically (P﹤0.01). The positive rates were respectively 33.33%、58.33%、86.96%、100.00% in T1 grade, T2 grade, T3 grade and T4 grade. There were notable significant difference among them statistically(P﹤0.01), The positive rates were respectively 33.33%、50.00%、85.00%、100.00% in I stage, II stage , III stage and IV stage. there were notable significant difference among them statistically(P﹤0.01).The positive rates were respectively 100%, 57.89% in have and without lymph node diversion, there were notable significant difference between them statistically(P﹤0.01)there are not significant difference statistically among different age, sex, tumour position.With increasing of T grade, clinical stage and lymph node diversion, the positive rates of IGF-1R were basically gradually increasing. With cutting down of histology differentiated degree, the positive rates of IGF-1R were basically gradually increasing. The positive rates of IGF-1R were 51.72% in the cases of PTEN positive expression, the positive rates of IGF-1R were 90.47% in the cases of PTEN negative expression; the positive rates of PTEN were 44.11% in the cases of IGF-1R positive expression, the positive rates of PTEN were 87.50% in the cases IGF-1R of positive expression. Through rank correlation analysis, r= -0.570 ,P=0.000. PTEN expression was obviously negative correlation with IGF-1R expression. Conclusions 1. The expression of PTEN protein is cutting down, the expression of IGF-1R protein is increasing , absence and/or deactivation of PTEN and overexpression of IGF-1R are probably playing a role in LSCC. 2. The expression of PTEN protein and IGF-1R protein are correlated with histology differentiated degree, T grade, clinical stage and lymph node diversion of LSCC. PTEN and IGF-1R probably play a role in occurrence, development, invasion and progress of LSCC, and their expression-level probably become mark to judge tumour’s malignant-degree. We can draw a conclusion that absence and/or deactivation of PTEN and overexpression of IGF-1R are probably section of disease mechanism. 3. The study show that PTEN protein is low-expression, IGF-1R protein is overexpression, and they are negative correlation, so we can infer that there is disequilibrium between PTEN and IGF-1R, and this disequilibrium probably play a role in LSCC.
引文
[1]黄选兆等主编.实用耳鼻咽喉头颈外科学,第2版.北京:人民卫生出版社,2007:488-490.
[2] McMahon S, Chen. Head and neck cancer. Cancer and metastasis rev, 2003, 22(1): 21-24.
[3]李丽,冯俊,唐嗣泉,等.喉癌癌基因研究进展.川北医学院学报, 2007,22(4):387-390.
[4] Parsons R.. Human cancer, PTEN and the PI-3 kinase pathway . Semin Cell Dev Biol, 2004, 15(2): 171-176.
[5]何龙,王继群,山艳春,等.抑癌基因PTEN在喉鳞状细胞癌和转移淋巴结中的表达.中国耳鼻咽喉头颈外科, 2005 ,12 (4 ): 235-238.
[6]王瑶,委阁. IGF-1R在宫颈癌和淋巴结转移组织中表达的临床意义.现代妇产科进展, 2007,16(2): 103-105.
[7] Li J, Yen C, Liaw D, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science, 1997, 275(5308): 1943-1947.
[8] Steck PA, Pershouse MA, Jasser SA, et al. Identidication of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet, 1997,15(4): 356-362.
[9] Li DM, Sun H. TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta. Cancer Res, 1997, 57(11): 2124-2129.
[10] Lee S, Choi EJ, Jin C, et al,. Activation of PI3K/Akt pathway by PTEN reduction and PIK3CA MRNA amplification contributes to cisplatin resistance in an ovarian cancer cell line. Gynecologic Oncology. 2005, 97 (1): 26-34.
[11] Chung JH, Eng C. Nuclear-cytoplasmic partitioning of phospha-tase and tensinhomologue deleted on chromosome 10 (PTEN) differentially regulates the cell cycle and apoptosis. Cancer Res,2005, 65(18): 8096-8100.
[12] Leslie NR, Yang X, Downes CP, et al. PtdIns(3, 4, 5)P(3)-dependent and-independent roles for PTEN in the control of cell migration. Curr Biol. 2007, 17(2): 115-125.
[13] Raftopoulou M, Etienne-Manneville S, Self A, et al. Regulation of cell migration by the C2 domain of the tumor suppressor PTEN. Science, 2004, 303(5661): 1179-1181.
[14] Shen WH, Balajee AS, Wang J, et al. Essential role for nuclear PTEN in maintaining chromosomal integrity. Cell. 2007, 128 (1): 157-170.
[15] Haier J, Nicolson GL. PTEN regulates tumor cell adhesion of cells under dynamic conditions of fluid. Oncogene,2002,21(9):1450-1460.
[16] Frisk T, Foukakis T, Dwinght T, et al. Silencing of the PTEN tumor-suppressor gene in anaplastic thyroid cancer. Genes Chromosomes Cancer,2002,35(1):74-80.
[17] Li L, Liu F, Ross AH. PTEN regulation of nueral development and CNS sten cell. Biochem,2003,88(1):24-28.
[18] Cary DS, Mattson MP. PTEN regulates Akt kinase activity in hippocampal neurons and increases their sensitivity to glutamate and apoptosis. Neuromolecular Med,2002,2(3): 261-269.
[19] Yamada KM, Araki M. Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis. J Cell Sci,2001,114(Pt 13):2375-82
[20] Li JY, Zheng HC, Yang L, et al. Altered expression of PTEN gene and LOH of its epigenetic microsatellite in gastric carcinoma. Zhonghua Zhong Liu Za Zhi, 2004, 26(7):389-92.
[21] Yamada KM, Araki M. Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis. J Cell Sci, 2001, 114(Pt 13):2375-2382.
[22] Mutter GL, Lin MC, Fitzgerald JT, et al. Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. Natl Cancer Inst, 2000,92(11):924-931.
[23]Yang L, Kuang LG, Zhang HC, et al. PTEN encoding product: a marker for tumorigenesis and progression of gastric carcinoma. World J Gastroenterol,2003, 9(1): 35-39.
[24] Davies MA, Kim SJ, Parikh NU, et al. Adenoviral-mediated expression of MMAC/PTEN inhibits proliferation and metastasis of human prostate cancer cells. Clin Cancer Res, 2002, 8(6): 1904-1914.
[25] Tachibana M, Shibakita M, Ohno S, et al. Expression and prognostic significance of PTEN product protein in patients with esophageal squamous cell carcinoma.Cancer,2002, 94(7): 1955-1960.
[26] Wang S, Gao J, Lei Q, et al . Prostate specific deletion of the murine Pten tumor suppressor gene leads tometastatic prostate cancer. Cancer Cell, 2003, 4(3): 209-221.
[27] Tanaka M, Rosser CJ, Grossman HB. PTEN gene therapy induces growth inhibition and increases efficacy of chemotherapy in prostate cancer. Cancer Detect Prev, 2005, 29(2): 170-174.
[28]李劲松,杨琨,王建军,等. PTEN蛋白在食管癌中的表达及临床意义.华中科技大学学报(医学版), 2006,35(5):623-625,629.
[29]张丹丹,郭琳,王强,等.胃癌组织中PTEN,MMP-9和Caspase-3表达的关系.世界华人消化杂志, 2006,14(15):1487-1492.
[30]李艳,王新允,刘婷,等.肺癌及癌前病变组织芯片中PTEN的表达及其意义.肿瘤, 2006,26(1):52-54.
[31]廖东卫,王莉,张新光,等. PTEN/PIK信号转导相关蛋白在非小细胞肺癌组织中的表达及其意义.癌症, 2006,25(10):1238-1242.
[32] Poetsch M, Lorenz G, Kleist B. Detection of new PTEN/MMAC1 mutations inhead and neck squamous cell carcinomas with loss of chromosome 10. Cancer Genet Cytogenet, 2002, 132(1):20-24.
[33] Lee JI, Soria JC, Hassan KA, et al. Loss of PTEN expression as a prognostic maker for tongue cancer. Arch Otolaryngol Head Neck Surg,2001, 127(11):1441-1445.
[34] Mayo LD, Dixon JE, Durden DL, et al. PTEN protects p53 from Mdm2 and sensitizes cancer cells to chemotherapy. J Bio Chem, 2002, 277(7):5484-5489.
[35] Huang H, Cheville JC, Pan Y, et al. PTEN induces chemosensitivity in PTEN-mutated prostate cancer cells by suppression of Bcl-2 expression. J Biol Chem, 2001, 276(42): 38830 -38836.
[36] Yuan XJ, Whang YE. PTEN sensilizes prostate cancer cells to death receptor mediated and drug induced apoptosis through a FADD dependent pathway. Oncogene, 2002, 21(2): 319 -327.
[37]Tanaka M, Koul D, Davies MA, et al. MMAC1/PTEN inhibits cell growth and induces chemosensitivity to doxorubicin in human bladder cancer cells. Onco gene, 2000, 19(47):5406 - 5412.
[38] Anai S, Goodison S, Shiverick K, et al. Combination of PTEN gene therapy and radiation inhibits the growth of human prostate cancer xenografts. Hum Gene Ther, 2006, 17(10):975- 984.
[39] Huang H, Cheville JC, Pan Y, et al. PTEN induces chemosensitivity in PTEN-mutated prostate cancer cells by suppression of Bcl-2 expression. J Biol Chem, 2001, 276(42):38830- 38836.
[40] Tanaka M, Rosser CJ, Grossman HB. PTEN gene therapy induces growth inhibition and increases efficacy of chemotherapy in prostate cancer. Cancer Detect Prev, 2005, 29(2):170- 174.
[41] Gomes CP, Andrade LA. PTEN and p53 expression in primary ovariancarcinomas: immunohistochemical study and discussion of pathogenetic mechanisms. Int J Gynecol Cancer, 2006, 16(1):254- 258.
[42]常明章,孙彦,周剑勇. PTEN在喉癌及癌旁组织中的表达及其临床意义.实用临床医学, 2006, 7(6):13-16.
[43]白伟良,任重,李国栋. PTEN基因在喉鳞癌中的表达及意义.中国医科大学学报, 2005,(6):238-239.
[44]吴先光,何淑华,沈志等.喉癌组织中抑癌基因PTEN的表达及意义.中国中西医结合耳鼻咽喉科杂志, 2005, 13(4):186-188.
[45]常傲霜,田禾,陈干美等.抑癌因子PTEN在喉鳞癌组织中的表达.贵阳医学院学报, 2006,31(2):98-100.
[46]吴强,庄坤,姚宪义,等. p53和PTEN的表达与喉癌颈淋巴结转移的相关性研究.哈尔滨医科大学学报.2006, 40(2):135-137.
[47]方宏才,李威.胰岛素样生长因子Ⅰ受体和肿瘤的关系.广东医学, 2007,28(9):1530-1532.
[48]武广彬,黄昌明.胰岛素样生长因子Ⅰ型受体肿瘤靶向治疗.国际肿瘤学杂志,2006,33(4):253-256.
[49]曾翔,张唯力. IGF家族和前列腺增生的研究进展.中国男科学杂志, 2007,21(10):65-67.
[50] Tanaka Y, Kobayashi H, Suzuki M, et al. Genetic downregulation of pregnancy associated plasma protein-A (PAPP-A) by bikunin reduces IGF-I-dependent Akt and Erk1/2 activation and subsequently reduces ovarian cancer cell growth, invasion and metastasis. Int J Cancer. 2004, 109(3):336-347.
[51] Remacle-Bonnet M, Garrouste F, Baillat G, et al. Membrane rafts segregate pro-from anti-apoptotic insulin-like growth factor-Ⅰreceptor signaling in colon carcinoma cells stimulated by members of the tumor necrosis factor superfamily. Am J Pathol, 2005, 167(3): 761-773.
[52]何振宇,管迅行. IGF-ⅠR表达与乳腺癌细胞放射抗拒的相关性.中华实用医学, 2004, 6(13): 44-46.
[53]陈照丽,王欣,黄秉仁. IGF系统的生物学功能与其与肿瘤的关系.国外医学分子生物学分册, 2003, 25(1): 34-37.
[54] Li L, Yu H, Schumacher F, et al. Relation of serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 to risk of prostate cancer (United States).Cancer Causes Control, 2003,14(8): 721-726
[55] Dupont J, LeRoith D. Insulin and insulin-like growth factor I receptors: similarities and differences in signal transduction. Horm Res, 2001, 55(Suppl 2): 22-26
[56] Samani AA, Brodt P. The receptor for the type 1 insulin-like growth factor and itsligands regulate multiple cellular functions that impact on metastasis. Surg Oncol Clin N Am, 2001, 10(2):289-312.
[57]李鹏胜,彭俊生,肖方联.胃癌及其转移淋巴结组织中胰岛素样生长因子-I的表达及其临床意义.实用癌症杂志,2006,21(6):579-581.
[58] Jiang Y, Wang L, Gong W, et al. A high expression level of insulin-like growth factor I receptor is associated with increased expression of transcription factor Sp1 and regional lymph node metastasis of human gastric cancer. Clin Exp Metastasis, 2004, 21(8):755-764.
[59] Peiro G, Lohse P, Mayr D,. et al. Insulin-like growth factor-I receptor and PTEN protein expression in endometrial carcinoma. Correlation with bax and bcl-2 expression, microsatellite instability status, and outcome. Am J Clin Pathol 2003, 120(1):78-85.
[60] Piestrzeniewicz-Ulanska D, Brys M, Semczuk A, et al. TGF-βsignaling is disrupted in endometrial-type endometrial cancinomas. Gynecologic oncology, 2004, 95(1):173-180.
[61] Lukanova A, Lundin E, Toniolo P, et al. Circulating levels of insulin-like growth factor-1 and risk of ovarian cancer. INt.J.cancer, 2002, 101(6):549-554
[62] Min Y, AdachiY, Yamamoto H, et al. Insulin-like growth factor I receptor blockade enhances chemotherapy and radiation responses and inhibits tumour growth in human gastric cancer xenografts. Gut, 2005, 54(5): 591-600.
[63] Shen MR,Hsu YM,Hsu KF,et al. Insulin-like growth factor 1 is a potent stimulator Of cervical cancer cell invasiveness and proliferation that is modulated by aανβ3 integrin signaling. Carcinogenesis, 2006, 27(5): 962-971
[64] Pavelic K, Bukovie D, Pavelic J. The role insulin-like growth factor 2 and its receptor in human tumors. Mol Med, 2002, 8(12):771-780
[65] Maloney EK, Mclaughlin JL, Dagdigian NE, et al. An anti-insulin-like growth factorⅠreceptor antibody that is a potent inhibitor of cancer cell proliferation[J]. Caneer Res, 2003, 63(16):5073-5083
[66]牛朝诗,傅先明,汪业汉,等.多聚凝胶介导IGF-IR反义寡核苷酸治疗体内胶质瘤的实验研究.中华神经外科杂志, 2004,20(5):357-361.
[67] Burtrum D, Zhu ZP, Lu D, et al. A fully human monoclonal to the Insulin-like growth factor I receptor blocks ligand-dependent signaling and inhibits huaman tumor growth in vivo. Cancer research, 2003, 63(24): 8912-8921
[68] Andrews DW, Resnicoff M, Flanders AE, et al. Results of a pilot study involving the use of an antisense oligodeoxynucleotide directed against the insulin-like growth factor type I receptor in malignant astrocytomas. J Clin Oncol, 2001, 19 (8): 2189 -2200.
[69] Benini S, Manara MC, Baldini N, et al. Inhibition of insulin-like growth factor I receptor increases the antitumor activity of doxorubicin and vincristine against Ewing’s sarcoma cells. Clin Cancer Res, 2001, 7 (6): 1790 -1797.
[70] Blum G, Gazit A, Levitzki A. Development of new IGF-1 receptor kinaseinhibitors using catechol mimics. JBiol Chem, 2003, 278 (42):40442-40454.
[71] Tang Y, Zhang D, Fallavollita L, et al. Vascular endothelial growth factor C expression and lymph node metastasis are regulated by the type I insulin-like growth factor receptor. Cancer Research, 2003, 63(6):1166-1171.
[72] Sun HZ, Wu SF, Tu ZH. Knockdown of IGF-IR by Antisense Oligodeoxynucleotide auguments the sensitivity of bladder cancer cells to Mitomycin. Acta Pharmacol Sin 2001, 22(9): 841-846.
[73] Konopka B, Janiec-Jankowska A, Czapczak D, et al. Molecular genetic defects in endometrial carcinomas: microsatellite instability, PTEN and betacatenin(CTNNB1) genes mutations. J Cancer Res Clin Oncol, 2007, 133(6): 361-371.
[74]季晨阳,刘来显,罗荣成,等.乳腺癌组织中胰岛素样生长因子I型受体的表达与病理学变化及预后的关系.中国临床康复, 2004,8:8003-8006.
[75]迟小岩,王言奎.子宫内膜癌组织IGF-1与其受体表达及意义.齐鲁医学杂志, 2008,23(3):198-203.
[76]车娜,葛荣明,陈玮伦. IGF-I、IGF-IR在喉鳞癌中的表达及意义.同济大学学报(医学版) , 2007 ,28(6):17-21.
[77] Luo J, Manning BD, Cantley LC. Targeting the PI3K-Akt pathway in human cancer: rationale and promise. Cancer Cell, 2003, 4(4):257-262
[78] Katso R, Okkenhaug K, Ahmadi K, et al. Cellular function of phosphoinositide 3 kinases:implications for development, homeostasis, and cancer. Annu Rev Cell Dev Biol, 2001, 17: 615-675
[79] Harris TK. PDK1 and PKB/Akt: ideal targets for development of new strategies to structure-based drug design. IDBMB Life, 2003, 55(3):117-126
[80] Stambolic V, Suzuki A, de la Pompa JL , et al . Negative regulation of PKB/Akt dependent cell survival by the tumor suppressor PTEN. Cell, 2001, 95(1) :29
[81] Leslie NR, Downes CP. PTEN function: how normal cells control it and tumour cells lose it. Biochem J, 2004, 382(PT1):1-11.
[82]王华芳,胡豫,孙春艳,等. MAPK途径磷酸化在胰岛素样生长因子-1促进人骨髓瘤细胞株KM3增殖中的作用.中国实验血液学杂志,2007,15(5):978 -981
[83]龚小卫,姜勇.丝裂原活化蛋白激酶启动蛋白激酶(MK)研究进展.生物化学与生物物理进展, 2007,34(7):695-701.
[84] Gaestel M. MAPKAP kinases - MKs - two’s company, three’s a crowd. Nat Rev Mol Cell Biol, 2006, 7 (2): 120-130
[85]高泽俊,袁小青,沈捷等. MAPKs通路在LePtin促人乳腺癌细胞系增殖中的机制研究.南京医科大学学报(自然科学版) , 2008,28(11):1410-1414.
[86] Zhao H, Dupont J, Yakar S, et al. PTEN inhibits cell proliferation and induces apoptosis by downregulating cell surface IGF-IR expression in prostate cancer cells. Oncogene, 2004, 23(3):786-94.
[87] Liao DW, Wang L, Zhang XG, et al. Expression and significance of PTEN/PI3K signal transduction-related proteins in non-small cell lung cancer. Ai Zheng, 2006, 25(10):1238-1242.
[88]赵雪峰,李勇,范立侨,等.胃癌及其区域淋巴结中PTEN、IGF-1/IGF-1RmRNA的表达.中国老年学杂志,2007,(04):736-738.
[89]刘新琼,彭树松,李晖晖,等.抑癌基因PTEN和胰岛素样生长因子-1受体在子宫内膜癌中的表达及临床意义.中国基层医药,2005,12(6):684-685.
[90] Yi HK, Kim SY, Hwang PH, et al. Impact of PTEN on the expression of insulin-like growth factors (IGFs) and IGF-binding proteins in human gastric adenocarcinoma cells. Biochem Biophys Res Commun. 2005, 330(3):760-767.
[91] Zhao H, Dupont J, Yakar S, et al. PTEN inhibits cell proliferation and induces apoptosis by downregulating cell surface IGF-IR expression in prostate cancer cells. Oncogene, 2004, 23(3):786-794.
[92]王群,林从尧,袁峰,等.胃腺癌中IGFⅠR的表达及与抑癌基因PTEN相关性的研究.武汉大学学报(医学版) , 2008,29(4):435-438.
[93]辛丽红,李雅莉. PTEN基因与肿瘤研究进展.陕西医学杂志, 2005,34(5):594-595.
[94] Bakiewicz A, Gozdzik J, Spomy S. PTEN gene expression in the endometrial mucosa. Ginekol Pol, 2006, 77(4):323-329.
[1] Sakurada A,Hamada H, Fukushige S,et al. Adenovirus-mediated delivery of the PTEN gene inhibits cell growth by induction of apoptosis in endometrial cancer. International Journal of Oncology, 1999, 15(6):1069- 1074.
[2] Reifenberger J,Wolter M, Bostrttm J, etal. Allelic losses on chromosome arm 10q and mutation of the PTEN/MMACl tumor suppressor gene in Primary and metastatic malignant melanomas. Virchows arch, 2000, 436: 487-493.
[3] Celebi JT, Shendrik I, Silvers Dn, etal. Identification of PTEN mutations in metastatic melanoma specimens. J Med Genet, 2000, 37: 653-657.
[4] Parsons R.. Human cancer, PTEN and the PI-3 kinase pathway. Semin Cell Dev Biol, 2004, 15(2): 171-176.
[5] Yoshimoto M, Cutz JC, Nuin PA, et al. Interphase FISH analysis of PTEN in histologic of sections shows genomic deletions in 68% of primary prostate cancer and 23% high-grade prosraticintra-epithelial neoplasias. Cancer Genet Cytogenet, 2006, 169(2):128- 137.
[6] Rasheed BK, Stenzel TT, Mclendon RE, et al. PTEN gene mutations are seen in high-grade but not in low grade gliomas. Cancer Res, 1997, 57(19): 4187-4190.
[7] Li J, Yen C, Liaw D, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science, 1997, 275(5308): 1943-1947.
[8] Steck PA, Pershouse MA, Jasser SA, et al. Identidication of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet, 1997, 15(4): 356-362.
[9] Li DM, Sun H. TEP1, encoded by a candidate tumor suppressor locus, is a novelprotein tyrosine phosphatase regulated by transforming growth factor beta. Cancer Res, 1997, 57(11): 2124-2129.
[10] Lee S, Choi EJ, Jin C, et al,. Activation of PI3K/Akt pathway by PTEN reduction and PIK3CA MRNA amplification contributes to cisplatin resistance in an ovarian cancer cell line. Gynecologic Oncology. 2005, 97 (1): 26-34.
[11] Chung JH, Eng C. Nuclear-cytoplasmic partitioning of phospha-tase and tensin homologue deleted on chromosome 10 (PTEN) differentially regulates the cell cycle and apoptosis. Cancer Res, 2005, 65(18): 8096-8100.
[12]Leslie NR, Yang X, Downes CP, et al. PtdIns (3, 4, 5)P(3)-dependent and-independent roles for PTEN in the control of cell migration. Curr Biol. 2007, 17(2): 115-125.
[13]Raftopoulou M, Etienne-Manneville S, Self A, et al. Regulation of cell migration by the C2 domain of the tumor suppressor PTEN. Science, 2004, 303(5661): 1179-1181.
[14]Shen WH, Balajee AS, Wang J, et al. Essential role for nuclear PTEN in maintaining chromosomal integrity. Cell. 2007, 128 (1): 157-170.
[15] Haier J, Nicolson GL. PTEN regulates tumor cell adhesion of cells under dynamic conditions of fluid. Oncogene, 2002, 21(9):1450-1460.
[16] Frisk T, Foukakis T, Dwinght T, et al. Silencing of the PTEN tumor-suppressor gene in anaplastic thyroid cancer. Genes Chromosomes Cancer, 2002, 35(1):74-80.
[17]Li L, Liu F, Ross AH. PTEN regulation of nueral development and CNS sten cell. Biochem, 2003, 88(1): 24-28.
[18] Cary DS, Mattson MP. PTEN regulates Akt kinase activity in hippocampal neurons and increases their sensitivity to glutamate and apoptosis. Neuromolecular Med, 2002, 2(3): 261-269.
[19] Yamada KM, Araki M. Tumor suppressor PTEN: modulator of cell signaling,growth, migration and apoptosis. J Cell Sci, 2001,114(Pt 13):2375-82
[20] Li JY, Zheng HC, Yang L, et al. Altered expression of PTEN gene and LOH of its epigenetic microsatellite in gastric carcinoma. Zhonghua Zhong Liu Za Zhi., 2004, 26(7):389-92.
[21] Yamada KM, Araki M. Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis. J Cell Sci, 2001, 114(Pt 13):2375-2382.
[22] Mutter GL, Lin MC, Fitzgerald JT, et al. Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. Natl Cancer Inst, 2000, 92(11):924-931.
[23]Yang L, Kuang LG, Zhang HC, et al. PTEN encoding product: a marker for tumorigenesis and progression of gastric carcinoma. World J Gastroenterol, 2003, 9(1): 35-39.
[24] Davies MA, Kim SJ, Parikh NU, et al. Adenoviral-mediated expression of MMAC/PTEN inhibits proliferation and metastasis of human prostate cancer cells. Clin Cancer Res, 2002, 8(6): 1904-1914.
[25] Tachibana M, Shibakita M, Ohno S, et al. Expression and prognostic significance of PTEN product protein in patients with esophageal squamous cell carcinoma.Cancer,2002, 94(7): 1955-1960.
[26]Wang S, Gao J, Lei Q, et al. Prostate specific deletion of the murine Pten tumor suppressor gene leads tometastatic prostate cancer. Cancer Cell, 2003, 4(3): 209-221.
[27]Tanaka M, Rosser CJ, Grossman HB. PTEN gene therapy induces growth inhibition and increases efficacy of chemotherapy in prostate cancer. Cancer Detect Prev, 2005, 29(2): 170-174.
[28]徐锡金,杨海伟,霍霞,等.抑癌基因PTEN在鼻咽癌组织中的表达及意义.临床耳鼻咽喉科杂志. 2004, 18(11):658-659.
[29] Davies MA,Kim SJ, Parikh NU, et al. Adenoviral-mediated expression ofMMAC/PTEN inhibits proliferation and metastasis of human prostate cancer cells. Clinical Cancer Research, 2002, 8(6):1904- 1914.
[30] Saito Y, Swanson X, Mhashilkar AM, et al. Adenovirus-mediated transfer of the PTEN gene inhibits human colorectal cancer growth in vitro and in vivo. Gene Therapy, 2003, 10(23):1961- 1969.
[31] Stewart AL, Mhashilkar AM, Yang XH, et al. PI3 kinase blockade by Ad-PTEN inhibits invasion and induces apoptosis in RGP and metastatic melanoma cells. Mol Med, 2002, 8(8):451- 461.
[32]Poetsch M, Lorenz G, Kleist B. Detection of new PTEN/MMAC1 mutations in head and neck squamous cell carcinomas with loss of chromosome 10. Cancer Genet Cytogenet, 2002, 132(1):20-24.
[33]Lee JI, Soria JC, Hassan KA, et al. Loss of PTEN expression as a prognostic maker for tongue cancer.Arch Otolaryngol Head Neck Surg,2001, 127(11):1441-1445.
[34]Mayo LD, Dixon JE, Durden DL, et al. PTEN protects p53 from Mdm2 and sensitizes cancer cells to chemotherapy. J Bio Chem, 2002, 277(7):5484-5489.
[35]Huang H, Cheville JC, Pan Y, et al. PTEN induces chemosensitivity in PTEN-mutated prostate cancer cells by suppression of Bcl-2 expression. J Biol Chem, 2001, 276(42): 38830 -38836.
[36]Yuan XJ, Whang YE. PTEN sensilizes prostate cancer cells to death receptor mediated and drug induced apoptosis through a FADD dependent pathway . Oncogene, 2002, 21(2): 319 -327.
[37]Tanaka M, Koul D, Davies MA, et al. MMAC1/PTEN inhibits cell growth and induces chemosensitivity to doxorubicin in human bladder cancer cells. Onco gene, 2000, 19(47):5406 - 5412.
[38] Anai S, Goodison S, Shiverick K, et al. Combination of PTEN gene therapy andradiation inhibits the growth of human prostate cancer xenografts. Hum Gene Ther, 2006, 17(10):975- 984.
[39] Huang H, Cheville JC, Pan Y, et al. PTEN induces chemosensitivity in PTEN-mutated prostate cancer cells by suppression of Bcl-2 expression. J Biol Chem, 2001, 276(42): 38830- 38836.
[41] Gomes CP, Andrade LA. PTEN and p53 expression in primary ovarian carcinomas: immunohistochemical study and discussion of pathogenetic mechanisms. Int J Gynecol Cancer, 2006, 16(1):254- 258.
[42]常明章,孙彦,周剑勇. PTEN在喉癌及癌旁组织中的表达及其临床意义.实用临床医学,2006, 7(6):13-16.
[43]白伟良,任重,李国栋. PTEN基因在喉鳞癌中的表达及意义.中国医科大学学报, 2005,(6):238-239.
[44]吴先光,何淑华,沈志等.喉癌组织中抑癌基因PTEN的表达及意义.中国中西医结合耳鼻咽喉科杂志, 2005, 13(4):186-188.
[45]常傲霜,田禾,陈干美等.抑癌因子PTEN在喉鳞癌组织中的表达.贵阳医学院学报, 2006,31(2):98-100.
[46]吴强,庄坤,姚宪义,等. p53和PTEN的表达与喉癌颈淋巴结转移的相关性研究.哈尔滨医科大学学报,2006, 40(2):135-137.
[47] Seki M, Iwakawa J, Cheng H, et al. p53 and PTEN/MMAC1/TEP1 gene therapy of human prostate PC-3 carcinoma xenograft, using transferrin-facilitated lipofection gene delivery strategy. Hum Gene Ther, 2002, 13(6):761- 773.
[48] Rosser CJ, Tanaka M, Pisters LL, et al. Adenoviral-mediated PTEN transgene expression sensitizes Bcl-2-expressing prostate cancer cells to radiation. Cancer Gene Therapy, 2004, 11(4):273- 279.
[49] Tian XX, Zhang YG, Du J, et al. Effects of cotransfection of antisense-EGFR and wild-type PTEN cDNA on human glioblastoma cells. Neuropathology, 2006,26(3): 178- 187.
[50] Tanaka M, Grossman HB. In vivo gene therapy of human bladder cancer with PTEN suppresses tumor growth, downregulates phosphorylated Akt, and increases sensitivity to doxorubicin. Gene Ther, 2003, 10(19):1636- 1642.
[51] Konopka B, Janiec-Jankowska A, Czapczak D, et al. Molecular genetic defects in endometrial carcinomas: microsatellite instability, PTEN and betacatenin(CTNNB1) genes mutations. J Cancer Res Clin Oncol, 2007, 133(6): 361-371.
[52]辛丽红,李雅莉. PTEN基因与肿瘤研究进展.陕西医学杂志, 2005,34(5):594-595.
[53] Bakiewicz A, Gozdzik J, Spomy S. PTEN gene expression in the endometrial mucosa. Ginekol Pol, 2006, 77(4):323-329.
[1] Del Valle L, Enam S, Lassak A, et al. Insulin-like growth factor I receptor activity in human medulloblastomas. Clin Cancer Res, 2002,8(6):1822-1830.
[2] VellaV, Sciacca L, Pandini G et al. The IGF system in thyroid cancer: new concepts. Mol Pathol. 2001, 54(3):121-124.
[3] Weber MM, Fottner C, Wolf E. The role of the insulin-like growth factor system in adrenocortical tumourigenesis. Eur J Clin Invest, 2000, 30 Suppl 3:69-75.
[4] Sachdev D, Li SL, Hartell JS, et al. A chimeric humanized single-chain antibody against the type I insulin-like growth factor ( IGF) receptor renders breast cancer cells refractory to the mitogenic effects of IGF-I. Cancer Res, 2003, 63(3):627-635.
[5] Resnicoff M. Antitumors effects elicited by antisense mediated down regulation of the insulin like growth factorI receptor. Int J Mol Med, 1998,l(5):883-888.
[6]王瑶,委阁. IGF-1R在宫颈癌和淋巴结转移组织中表达的临床意义.现代妇产科进展, 2007,16(2): 103-105.
[7]方宏才,李威.胰岛素样生长因子1受体和肿瘤的关系.广东医学, 2007,28(9):1530-1532.
[8]武广彬,黄昌明.胰岛素样生长因子1型受体肿瘤靶向治疗.国际肿瘤学杂志,2006,33(4):253-256.
[9]曾翔,张唯力. IGF家族和前列腺增生的研究进展.中国男科学杂志, 2007,21(10):65-67.
[10] Tanaka Y, Kobayashi H, Suzuki M, et al. Genetic downregulation of pregnancy associated plasma protein-A (PAPP-A) by bikunin reduces IGF-I-dependent Akt and Erk1/2 activation and subsequently reduces ovarian cancer cell growth,invasion and metastasis. Int J Cancer, 2004, 109(3): 336-347.
[11] Remacle-Bonnet M, Garrouste F, Baillat G, et al. Membrane rafts segregate pro-from anti-apoptotic insulin-like growth factor-Ⅰreceptor signaling in colon carcinoma cells stimulated by members of the tumor necrosis factor superfamily. Am J Pathol, 2005, 167(3): 761-773.
[12]何振宇,管迅行. IGF-1R表达与乳腺癌细胞放射抗拒的相关性.中华实用医学, 2004, 6(13): 44-46.
[13]陈照丽,王欣,黄秉仁. IGF系统的生物学功能与其与肿瘤的关系.国外医学分子生物学分册, 2003, 25(1): 34-37.
[14] Li L, Yu H, Schumacher F, et al. Relation of serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 to risk of prostate cancer (United States).Cancer Causes Control, 2003,14(8): 721-726.
[15] Dupont J, LeRoith D. Insulin and insulin-like growth factor I receptors: similarities and differences in signal transduction. Horm Res, 2001, 55(Suppl 2): 22-26.
[16] Samani AA, Brodt P. The receptor for the type 1 insulin-like growth factor and its ligands regulate multiple cellular functions that impact on metastasis. Surg Oncol Clin N Am, 2001, 10(2):289-312.
[17]李鹏胜,彭俊生,肖方联.胃癌及其转移淋巴结组织中胰岛素样生长因子-I的表达及其临床意义.实用癌症杂志, 2006,21(6):579-581.
[18] Jiang Y, Wang L, Gong W, et al. A high expression level of insulin-like growth factor I receptor is associated with increased expression of transcription factor Sp1 and regional lymph node metastasis of human gastric cancer. Clin Exp Metastasis, 2004, 21(8):755-764.
[19] Peiro G, Lohse P, Mayr D, et al. Insulin-like growth factor-I receptor and PTEN protein expression in endometrial carcinoma. Correlation with bax and bcl-2expression, microsatellite instability status, and outcome. Am J Clin Pathol, 2003, 120(1): 78-85.
[20] Piestrzeniewicz-Ulanska D, Brys M, Semczuk A, et al. TGF-βsignaling is disrupted in endometrial-type endometrial cancinomas. Gynecologic oncology, 2004, 95(1):173-180.
[21] Lukanova A, Lundin E, Toniolo P, et al. Circulating levels of insulin-like growth factor-1 and risk of ovarian cancer. INt.J.cancer, 2002, 101(6): 549-554
[22] Min Y, AdachiY, Yamamoto H, et al. Insulin-like growth factor I receptor blockade enhances chemotherapy and radiation responses and inhibits tumour growth in human gastric cancer xenografts. Gut, 2005, 54(5): 591-600.
[23] Shen MR,Hsu YM,Hsu KF,et al. Insulin-like growth factor 1 is a potent stimulator Of cervical cancer cell invasiveness and proliferation that is modulated by aανβ3 integrin signaling. Carcinogenesis, 2006, 27(5): 962-971
[24]Pavelic K, Bukovie D, Pavelic J. The role insulin-like growth factor 2 and its receptor in human tumors. Mol Med, 2002, 8(12):771-780
[25]Maloney EK, Mclaughlin JL, Dagdigian NE, et al. An anti-insulin-like growth factor I receptor antibody that is a potent inhibitor of cancer cell proliferation. Caneer Res, 2003, 63(16):5073-5083
[26]牛朝诗,傅先明,汪业汉,等.多聚凝胶介导IGF-IR反义寡核苷酸治疗体内胶质瘤的实验研究.中华神经外科杂志, 2004,20(5):357-361.
[27] Burtrum D, Zhu ZP, Lu D, et al. A fully human monoclonal to the Insulin-like growth factor I receptor blocks ligand-dependent signaling and inhibits huaman tumor growth in vivo. Cancer research, 2003, 63(24): 8912-8921
[28] Andrews DW, Resnicoff M, Flanders AE,et al. Results of a pilot study involving the use of an antisense oligodeoxynucleotide directed against the insulin-like growth factor type I receptor in malignant astrocytomas. J Clin Oncol, 2001, 19(8): 2189 -2200.
[29] Benini S, Manara MC, Baldini N, et al. Inhibition of insulin-like growth factor I receptor increases the antitumor activity of doxorubicin and vincristine against Ewing’s sarcoma cells. Clin Cancer Res, 2001, 7 (6): 1790 -1797.
[30] Blum G, Gazit A, Levitzki A. Development of new IGF-1 receptor kinase inhibitors using catechol mimics . JBiol Chem, 2003, 278 (42):40442-40454.
[31]Tang Y, Zhang D, Fallavollita L, et al. Vascular endothelial growth factor C expression and lymph node metastasis are regulated by the type I insulin-like growth factor receptor. Cancer Research, 2003, 63(6):1166-1171.
[32]Sun HZ , Wu SF , Tu ZH. Knockdown of IGF-IR by Antisense Oligodeoxynucleotide auguments the sensitivity of bladder cancer cells to Mitomycin. Acta Pharmacol Sin 2001, 22(9): 841-846.
[33] Camirand A, Lu Y, Pollak M. Co targeting HER2/ErbB2 and insulin-like growth factor-1 receptors causes synergistic inhibition of growth in HER2 overexpressing breast cancer cells. Med Sci Monit, 2002, 8(12): BR521-526.
[34]季晨阳,刘来显,罗荣成,等.乳腺癌组织中胰岛素样生长因子1型受体的表达与病理学变化及预后的关系.中国临床康复, 2004,8:8003-8006.
[35]迟小岩,王言奎.子宫内膜癌组织IGF-1与其受体表达及意义.齐鲁医学杂志, 2008,23(3):198-203.
[36]车娜,葛荣明,陈玮伦. IGF-1、IGF-1R在喉鳞癌中的表达及意义.同济大学学报(医学版) , 2007 ,28(6):17-21.
[37] DuPont J, Le Roith D. Insulin-like growth factor I and oestradiol promote cell proliferation of MCF-7 breast cancer cells: new insights into their synergistic effects. Mol Pathol. 2001, 54(3):149 154.
[2] McMahon S, Chen. Head and neck cancer. Cancer and metastasis rev, 2003, 22(1): 21-24.
[3]李丽,冯俊,唐嗣泉,等.喉癌癌基因研究进展.川北医学院学报, 2007,22(4):387-390.
[4] Parsons R.. Human cancer, PTEN and the PI-3 kinase pathway . Semin Cell Dev Biol, 2004, 15(2): 171-176.
[5]何龙,王继群,山艳春,等.抑癌基因PTEN在喉鳞状细胞癌和转移淋巴结中的表达.中国耳鼻咽喉头颈外科, 2005 ,12 (4 ): 235-238.
[6]王瑶,委阁. IGF-1R在宫颈癌和淋巴结转移组织中表达的临床意义.现代妇产科进展, 2007,16(2): 103-105.
[7] Li J, Yen C, Liaw D, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science, 1997, 275(5308): 1943-1947.
[8] Steck PA, Pershouse MA, Jasser SA, et al. Identidication of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet, 1997,15(4): 356-362.
[9] Li DM, Sun H. TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta. Cancer Res, 1997, 57(11): 2124-2129.
[10] Lee S, Choi EJ, Jin C, et al,. Activation of PI3K/Akt pathway by PTEN reduction and PIK3CA MRNA amplification contributes to cisplatin resistance in an ovarian cancer cell line. Gynecologic Oncology. 2005, 97 (1): 26-34.
[11] Chung JH, Eng C. Nuclear-cytoplasmic partitioning of phospha-tase and tensinhomologue deleted on chromosome 10 (PTEN) differentially regulates the cell cycle and apoptosis. Cancer Res,2005, 65(18): 8096-8100.
[12] Leslie NR, Yang X, Downes CP, et al. PtdIns(3, 4, 5)P(3)-dependent and-independent roles for PTEN in the control of cell migration. Curr Biol. 2007, 17(2): 115-125.
[13] Raftopoulou M, Etienne-Manneville S, Self A, et al. Regulation of cell migration by the C2 domain of the tumor suppressor PTEN. Science, 2004, 303(5661): 1179-1181.
[14] Shen WH, Balajee AS, Wang J, et al. Essential role for nuclear PTEN in maintaining chromosomal integrity. Cell. 2007, 128 (1): 157-170.
[15] Haier J, Nicolson GL. PTEN regulates tumor cell adhesion of cells under dynamic conditions of fluid. Oncogene,2002,21(9):1450-1460.
[16] Frisk T, Foukakis T, Dwinght T, et al. Silencing of the PTEN tumor-suppressor gene in anaplastic thyroid cancer. Genes Chromosomes Cancer,2002,35(1):74-80.
[17] Li L, Liu F, Ross AH. PTEN regulation of nueral development and CNS sten cell. Biochem,2003,88(1):24-28.
[18] Cary DS, Mattson MP. PTEN regulates Akt kinase activity in hippocampal neurons and increases their sensitivity to glutamate and apoptosis. Neuromolecular Med,2002,2(3): 261-269.
[19] Yamada KM, Araki M. Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis. J Cell Sci,2001,114(Pt 13):2375-82
[20] Li JY, Zheng HC, Yang L, et al. Altered expression of PTEN gene and LOH of its epigenetic microsatellite in gastric carcinoma. Zhonghua Zhong Liu Za Zhi, 2004, 26(7):389-92.
[21] Yamada KM, Araki M. Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis. J Cell Sci, 2001, 114(Pt 13):2375-2382.
[22] Mutter GL, Lin MC, Fitzgerald JT, et al. Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. Natl Cancer Inst, 2000,92(11):924-931.
[23]Yang L, Kuang LG, Zhang HC, et al. PTEN encoding product: a marker for tumorigenesis and progression of gastric carcinoma. World J Gastroenterol,2003, 9(1): 35-39.
[24] Davies MA, Kim SJ, Parikh NU, et al. Adenoviral-mediated expression of MMAC/PTEN inhibits proliferation and metastasis of human prostate cancer cells. Clin Cancer Res, 2002, 8(6): 1904-1914.
[25] Tachibana M, Shibakita M, Ohno S, et al. Expression and prognostic significance of PTEN product protein in patients with esophageal squamous cell carcinoma.Cancer,2002, 94(7): 1955-1960.
[26] Wang S, Gao J, Lei Q, et al . Prostate specific deletion of the murine Pten tumor suppressor gene leads tometastatic prostate cancer. Cancer Cell, 2003, 4(3): 209-221.
[27] Tanaka M, Rosser CJ, Grossman HB. PTEN gene therapy induces growth inhibition and increases efficacy of chemotherapy in prostate cancer. Cancer Detect Prev, 2005, 29(2): 170-174.
[28]李劲松,杨琨,王建军,等. PTEN蛋白在食管癌中的表达及临床意义.华中科技大学学报(医学版), 2006,35(5):623-625,629.
[29]张丹丹,郭琳,王强,等.胃癌组织中PTEN,MMP-9和Caspase-3表达的关系.世界华人消化杂志, 2006,14(15):1487-1492.
[30]李艳,王新允,刘婷,等.肺癌及癌前病变组织芯片中PTEN的表达及其意义.肿瘤, 2006,26(1):52-54.
[31]廖东卫,王莉,张新光,等. PTEN/PIK信号转导相关蛋白在非小细胞肺癌组织中的表达及其意义.癌症, 2006,25(10):1238-1242.
[32] Poetsch M, Lorenz G, Kleist B. Detection of new PTEN/MMAC1 mutations inhead and neck squamous cell carcinomas with loss of chromosome 10. Cancer Genet Cytogenet, 2002, 132(1):20-24.
[33] Lee JI, Soria JC, Hassan KA, et al. Loss of PTEN expression as a prognostic maker for tongue cancer. Arch Otolaryngol Head Neck Surg,2001, 127(11):1441-1445.
[34] Mayo LD, Dixon JE, Durden DL, et al. PTEN protects p53 from Mdm2 and sensitizes cancer cells to chemotherapy. J Bio Chem, 2002, 277(7):5484-5489.
[35] Huang H, Cheville JC, Pan Y, et al. PTEN induces chemosensitivity in PTEN-mutated prostate cancer cells by suppression of Bcl-2 expression. J Biol Chem, 2001, 276(42): 38830 -38836.
[36] Yuan XJ, Whang YE. PTEN sensilizes prostate cancer cells to death receptor mediated and drug induced apoptosis through a FADD dependent pathway. Oncogene, 2002, 21(2): 319 -327.
[37]Tanaka M, Koul D, Davies MA, et al. MMAC1/PTEN inhibits cell growth and induces chemosensitivity to doxorubicin in human bladder cancer cells. Onco gene, 2000, 19(47):5406 - 5412.
[38] Anai S, Goodison S, Shiverick K, et al. Combination of PTEN gene therapy and radiation inhibits the growth of human prostate cancer xenografts. Hum Gene Ther, 2006, 17(10):975- 984.
[39] Huang H, Cheville JC, Pan Y, et al. PTEN induces chemosensitivity in PTEN-mutated prostate cancer cells by suppression of Bcl-2 expression. J Biol Chem, 2001, 276(42):38830- 38836.
[40] Tanaka M, Rosser CJ, Grossman HB. PTEN gene therapy induces growth inhibition and increases efficacy of chemotherapy in prostate cancer. Cancer Detect Prev, 2005, 29(2):170- 174.
[41] Gomes CP, Andrade LA. PTEN and p53 expression in primary ovariancarcinomas: immunohistochemical study and discussion of pathogenetic mechanisms. Int J Gynecol Cancer, 2006, 16(1):254- 258.
[42]常明章,孙彦,周剑勇. PTEN在喉癌及癌旁组织中的表达及其临床意义.实用临床医学, 2006, 7(6):13-16.
[43]白伟良,任重,李国栋. PTEN基因在喉鳞癌中的表达及意义.中国医科大学学报, 2005,(6):238-239.
[44]吴先光,何淑华,沈志等.喉癌组织中抑癌基因PTEN的表达及意义.中国中西医结合耳鼻咽喉科杂志, 2005, 13(4):186-188.
[45]常傲霜,田禾,陈干美等.抑癌因子PTEN在喉鳞癌组织中的表达.贵阳医学院学报, 2006,31(2):98-100.
[46]吴强,庄坤,姚宪义,等. p53和PTEN的表达与喉癌颈淋巴结转移的相关性研究.哈尔滨医科大学学报.2006, 40(2):135-137.
[47]方宏才,李威.胰岛素样生长因子Ⅰ受体和肿瘤的关系.广东医学, 2007,28(9):1530-1532.
[48]武广彬,黄昌明.胰岛素样生长因子Ⅰ型受体肿瘤靶向治疗.国际肿瘤学杂志,2006,33(4):253-256.
[49]曾翔,张唯力. IGF家族和前列腺增生的研究进展.中国男科学杂志, 2007,21(10):65-67.
[50] Tanaka Y, Kobayashi H, Suzuki M, et al. Genetic downregulation of pregnancy associated plasma protein-A (PAPP-A) by bikunin reduces IGF-I-dependent Akt and Erk1/2 activation and subsequently reduces ovarian cancer cell growth, invasion and metastasis. Int J Cancer. 2004, 109(3):336-347.
[51] Remacle-Bonnet M, Garrouste F, Baillat G, et al. Membrane rafts segregate pro-from anti-apoptotic insulin-like growth factor-Ⅰreceptor signaling in colon carcinoma cells stimulated by members of the tumor necrosis factor superfamily. Am J Pathol, 2005, 167(3): 761-773.
[52]何振宇,管迅行. IGF-ⅠR表达与乳腺癌细胞放射抗拒的相关性.中华实用医学, 2004, 6(13): 44-46.
[53]陈照丽,王欣,黄秉仁. IGF系统的生物学功能与其与肿瘤的关系.国外医学分子生物学分册, 2003, 25(1): 34-37.
[54] Li L, Yu H, Schumacher F, et al. Relation of serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 to risk of prostate cancer (United States).Cancer Causes Control, 2003,14(8): 721-726
[55] Dupont J, LeRoith D. Insulin and insulin-like growth factor I receptors: similarities and differences in signal transduction. Horm Res, 2001, 55(Suppl 2): 22-26
[56] Samani AA, Brodt P. The receptor for the type 1 insulin-like growth factor and itsligands regulate multiple cellular functions that impact on metastasis. Surg Oncol Clin N Am, 2001, 10(2):289-312.
[57]李鹏胜,彭俊生,肖方联.胃癌及其转移淋巴结组织中胰岛素样生长因子-I的表达及其临床意义.实用癌症杂志,2006,21(6):579-581.
[58] Jiang Y, Wang L, Gong W, et al. A high expression level of insulin-like growth factor I receptor is associated with increased expression of transcription factor Sp1 and regional lymph node metastasis of human gastric cancer. Clin Exp Metastasis, 2004, 21(8):755-764.
[59] Peiro G, Lohse P, Mayr D,. et al. Insulin-like growth factor-I receptor and PTEN protein expression in endometrial carcinoma. Correlation with bax and bcl-2 expression, microsatellite instability status, and outcome. Am J Clin Pathol 2003, 120(1):78-85.
[60] Piestrzeniewicz-Ulanska D, Brys M, Semczuk A, et al. TGF-βsignaling is disrupted in endometrial-type endometrial cancinomas. Gynecologic oncology, 2004, 95(1):173-180.
[61] Lukanova A, Lundin E, Toniolo P, et al. Circulating levels of insulin-like growth factor-1 and risk of ovarian cancer. INt.J.cancer, 2002, 101(6):549-554
[62] Min Y, AdachiY, Yamamoto H, et al. Insulin-like growth factor I receptor blockade enhances chemotherapy and radiation responses and inhibits tumour growth in human gastric cancer xenografts. Gut, 2005, 54(5): 591-600.
[63] Shen MR,Hsu YM,Hsu KF,et al. Insulin-like growth factor 1 is a potent stimulator Of cervical cancer cell invasiveness and proliferation that is modulated by aανβ3 integrin signaling. Carcinogenesis, 2006, 27(5): 962-971
[64] Pavelic K, Bukovie D, Pavelic J. The role insulin-like growth factor 2 and its receptor in human tumors. Mol Med, 2002, 8(12):771-780
[65] Maloney EK, Mclaughlin JL, Dagdigian NE, et al. An anti-insulin-like growth factorⅠreceptor antibody that is a potent inhibitor of cancer cell proliferation[J]. Caneer Res, 2003, 63(16):5073-5083
[66]牛朝诗,傅先明,汪业汉,等.多聚凝胶介导IGF-IR反义寡核苷酸治疗体内胶质瘤的实验研究.中华神经外科杂志, 2004,20(5):357-361.
[67] Burtrum D, Zhu ZP, Lu D, et al. A fully human monoclonal to the Insulin-like growth factor I receptor blocks ligand-dependent signaling and inhibits huaman tumor growth in vivo. Cancer research, 2003, 63(24): 8912-8921
[68] Andrews DW, Resnicoff M, Flanders AE, et al. Results of a pilot study involving the use of an antisense oligodeoxynucleotide directed against the insulin-like growth factor type I receptor in malignant astrocytomas. J Clin Oncol, 2001, 19 (8): 2189 -2200.
[69] Benini S, Manara MC, Baldini N, et al. Inhibition of insulin-like growth factor I receptor increases the antitumor activity of doxorubicin and vincristine against Ewing’s sarcoma cells. Clin Cancer Res, 2001, 7 (6): 1790 -1797.
[70] Blum G, Gazit A, Levitzki A. Development of new IGF-1 receptor kinaseinhibitors using catechol mimics. JBiol Chem, 2003, 278 (42):40442-40454.
[71] Tang Y, Zhang D, Fallavollita L, et al. Vascular endothelial growth factor C expression and lymph node metastasis are regulated by the type I insulin-like growth factor receptor. Cancer Research, 2003, 63(6):1166-1171.
[72] Sun HZ, Wu SF, Tu ZH. Knockdown of IGF-IR by Antisense Oligodeoxynucleotide auguments the sensitivity of bladder cancer cells to Mitomycin. Acta Pharmacol Sin 2001, 22(9): 841-846.
[73] Konopka B, Janiec-Jankowska A, Czapczak D, et al. Molecular genetic defects in endometrial carcinomas: microsatellite instability, PTEN and betacatenin(CTNNB1) genes mutations. J Cancer Res Clin Oncol, 2007, 133(6): 361-371.
[74]季晨阳,刘来显,罗荣成,等.乳腺癌组织中胰岛素样生长因子I型受体的表达与病理学变化及预后的关系.中国临床康复, 2004,8:8003-8006.
[75]迟小岩,王言奎.子宫内膜癌组织IGF-1与其受体表达及意义.齐鲁医学杂志, 2008,23(3):198-203.
[76]车娜,葛荣明,陈玮伦. IGF-I、IGF-IR在喉鳞癌中的表达及意义.同济大学学报(医学版) , 2007 ,28(6):17-21.
[77] Luo J, Manning BD, Cantley LC. Targeting the PI3K-Akt pathway in human cancer: rationale and promise. Cancer Cell, 2003, 4(4):257-262
[78] Katso R, Okkenhaug K, Ahmadi K, et al. Cellular function of phosphoinositide 3 kinases:implications for development, homeostasis, and cancer. Annu Rev Cell Dev Biol, 2001, 17: 615-675
[79] Harris TK. PDK1 and PKB/Akt: ideal targets for development of new strategies to structure-based drug design. IDBMB Life, 2003, 55(3):117-126
[80] Stambolic V, Suzuki A, de la Pompa JL , et al . Negative regulation of PKB/Akt dependent cell survival by the tumor suppressor PTEN. Cell, 2001, 95(1) :29
[81] Leslie NR, Downes CP. PTEN function: how normal cells control it and tumour cells lose it. Biochem J, 2004, 382(PT1):1-11.
[82]王华芳,胡豫,孙春艳,等. MAPK途径磷酸化在胰岛素样生长因子-1促进人骨髓瘤细胞株KM3增殖中的作用.中国实验血液学杂志,2007,15(5):978 -981
[83]龚小卫,姜勇.丝裂原活化蛋白激酶启动蛋白激酶(MK)研究进展.生物化学与生物物理进展, 2007,34(7):695-701.
[84] Gaestel M. MAPKAP kinases - MKs - two’s company, three’s a crowd. Nat Rev Mol Cell Biol, 2006, 7 (2): 120-130
[85]高泽俊,袁小青,沈捷等. MAPKs通路在LePtin促人乳腺癌细胞系增殖中的机制研究.南京医科大学学报(自然科学版) , 2008,28(11):1410-1414.
[86] Zhao H, Dupont J, Yakar S, et al. PTEN inhibits cell proliferation and induces apoptosis by downregulating cell surface IGF-IR expression in prostate cancer cells. Oncogene, 2004, 23(3):786-94.
[87] Liao DW, Wang L, Zhang XG, et al. Expression and significance of PTEN/PI3K signal transduction-related proteins in non-small cell lung cancer. Ai Zheng, 2006, 25(10):1238-1242.
[88]赵雪峰,李勇,范立侨,等.胃癌及其区域淋巴结中PTEN、IGF-1/IGF-1RmRNA的表达.中国老年学杂志,2007,(04):736-738.
[89]刘新琼,彭树松,李晖晖,等.抑癌基因PTEN和胰岛素样生长因子-1受体在子宫内膜癌中的表达及临床意义.中国基层医药,2005,12(6):684-685.
[90] Yi HK, Kim SY, Hwang PH, et al. Impact of PTEN on the expression of insulin-like growth factors (IGFs) and IGF-binding proteins in human gastric adenocarcinoma cells. Biochem Biophys Res Commun. 2005, 330(3):760-767.
[91] Zhao H, Dupont J, Yakar S, et al. PTEN inhibits cell proliferation and induces apoptosis by downregulating cell surface IGF-IR expression in prostate cancer cells. Oncogene, 2004, 23(3):786-794.
[92]王群,林从尧,袁峰,等.胃腺癌中IGFⅠR的表达及与抑癌基因PTEN相关性的研究.武汉大学学报(医学版) , 2008,29(4):435-438.
[93]辛丽红,李雅莉. PTEN基因与肿瘤研究进展.陕西医学杂志, 2005,34(5):594-595.
[94] Bakiewicz A, Gozdzik J, Spomy S. PTEN gene expression in the endometrial mucosa. Ginekol Pol, 2006, 77(4):323-329.
[1] Sakurada A,Hamada H, Fukushige S,et al. Adenovirus-mediated delivery of the PTEN gene inhibits cell growth by induction of apoptosis in endometrial cancer. International Journal of Oncology, 1999, 15(6):1069- 1074.
[2] Reifenberger J,Wolter M, Bostrttm J, etal. Allelic losses on chromosome arm 10q and mutation of the PTEN/MMACl tumor suppressor gene in Primary and metastatic malignant melanomas. Virchows arch, 2000, 436: 487-493.
[3] Celebi JT, Shendrik I, Silvers Dn, etal. Identification of PTEN mutations in metastatic melanoma specimens. J Med Genet, 2000, 37: 653-657.
[4] Parsons R.. Human cancer, PTEN and the PI-3 kinase pathway. Semin Cell Dev Biol, 2004, 15(2): 171-176.
[5] Yoshimoto M, Cutz JC, Nuin PA, et al. Interphase FISH analysis of PTEN in histologic of sections shows genomic deletions in 68% of primary prostate cancer and 23% high-grade prosraticintra-epithelial neoplasias. Cancer Genet Cytogenet, 2006, 169(2):128- 137.
[6] Rasheed BK, Stenzel TT, Mclendon RE, et al. PTEN gene mutations are seen in high-grade but not in low grade gliomas. Cancer Res, 1997, 57(19): 4187-4190.
[7] Li J, Yen C, Liaw D, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science, 1997, 275(5308): 1943-1947.
[8] Steck PA, Pershouse MA, Jasser SA, et al. Identidication of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet, 1997, 15(4): 356-362.
[9] Li DM, Sun H. TEP1, encoded by a candidate tumor suppressor locus, is a novelprotein tyrosine phosphatase regulated by transforming growth factor beta. Cancer Res, 1997, 57(11): 2124-2129.
[10] Lee S, Choi EJ, Jin C, et al,. Activation of PI3K/Akt pathway by PTEN reduction and PIK3CA MRNA amplification contributes to cisplatin resistance in an ovarian cancer cell line. Gynecologic Oncology. 2005, 97 (1): 26-34.
[11] Chung JH, Eng C. Nuclear-cytoplasmic partitioning of phospha-tase and tensin homologue deleted on chromosome 10 (PTEN) differentially regulates the cell cycle and apoptosis. Cancer Res, 2005, 65(18): 8096-8100.
[12]Leslie NR, Yang X, Downes CP, et al. PtdIns (3, 4, 5)P(3)-dependent and-independent roles for PTEN in the control of cell migration. Curr Biol. 2007, 17(2): 115-125.
[13]Raftopoulou M, Etienne-Manneville S, Self A, et al. Regulation of cell migration by the C2 domain of the tumor suppressor PTEN. Science, 2004, 303(5661): 1179-1181.
[14]Shen WH, Balajee AS, Wang J, et al. Essential role for nuclear PTEN in maintaining chromosomal integrity. Cell. 2007, 128 (1): 157-170.
[15] Haier J, Nicolson GL. PTEN regulates tumor cell adhesion of cells under dynamic conditions of fluid. Oncogene, 2002, 21(9):1450-1460.
[16] Frisk T, Foukakis T, Dwinght T, et al. Silencing of the PTEN tumor-suppressor gene in anaplastic thyroid cancer. Genes Chromosomes Cancer, 2002, 35(1):74-80.
[17]Li L, Liu F, Ross AH. PTEN regulation of nueral development and CNS sten cell. Biochem, 2003, 88(1): 24-28.
[18] Cary DS, Mattson MP. PTEN regulates Akt kinase activity in hippocampal neurons and increases their sensitivity to glutamate and apoptosis. Neuromolecular Med, 2002, 2(3): 261-269.
[19] Yamada KM, Araki M. Tumor suppressor PTEN: modulator of cell signaling,growth, migration and apoptosis. J Cell Sci, 2001,114(Pt 13):2375-82
[20] Li JY, Zheng HC, Yang L, et al. Altered expression of PTEN gene and LOH of its epigenetic microsatellite in gastric carcinoma. Zhonghua Zhong Liu Za Zhi., 2004, 26(7):389-92.
[21] Yamada KM, Araki M. Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis. J Cell Sci, 2001, 114(Pt 13):2375-2382.
[22] Mutter GL, Lin MC, Fitzgerald JT, et al. Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. Natl Cancer Inst, 2000, 92(11):924-931.
[23]Yang L, Kuang LG, Zhang HC, et al. PTEN encoding product: a marker for tumorigenesis and progression of gastric carcinoma. World J Gastroenterol, 2003, 9(1): 35-39.
[24] Davies MA, Kim SJ, Parikh NU, et al. Adenoviral-mediated expression of MMAC/PTEN inhibits proliferation and metastasis of human prostate cancer cells. Clin Cancer Res, 2002, 8(6): 1904-1914.
[25] Tachibana M, Shibakita M, Ohno S, et al. Expression and prognostic significance of PTEN product protein in patients with esophageal squamous cell carcinoma.Cancer,2002, 94(7): 1955-1960.
[26]Wang S, Gao J, Lei Q, et al. Prostate specific deletion of the murine Pten tumor suppressor gene leads tometastatic prostate cancer. Cancer Cell, 2003, 4(3): 209-221.
[27]Tanaka M, Rosser CJ, Grossman HB. PTEN gene therapy induces growth inhibition and increases efficacy of chemotherapy in prostate cancer. Cancer Detect Prev, 2005, 29(2): 170-174.
[28]徐锡金,杨海伟,霍霞,等.抑癌基因PTEN在鼻咽癌组织中的表达及意义.临床耳鼻咽喉科杂志. 2004, 18(11):658-659.
[29] Davies MA,Kim SJ, Parikh NU, et al. Adenoviral-mediated expression ofMMAC/PTEN inhibits proliferation and metastasis of human prostate cancer cells. Clinical Cancer Research, 2002, 8(6):1904- 1914.
[30] Saito Y, Swanson X, Mhashilkar AM, et al. Adenovirus-mediated transfer of the PTEN gene inhibits human colorectal cancer growth in vitro and in vivo. Gene Therapy, 2003, 10(23):1961- 1969.
[31] Stewart AL, Mhashilkar AM, Yang XH, et al. PI3 kinase blockade by Ad-PTEN inhibits invasion and induces apoptosis in RGP and metastatic melanoma cells. Mol Med, 2002, 8(8):451- 461.
[32]Poetsch M, Lorenz G, Kleist B. Detection of new PTEN/MMAC1 mutations in head and neck squamous cell carcinomas with loss of chromosome 10. Cancer Genet Cytogenet, 2002, 132(1):20-24.
[33]Lee JI, Soria JC, Hassan KA, et al. Loss of PTEN expression as a prognostic maker for tongue cancer.Arch Otolaryngol Head Neck Surg,2001, 127(11):1441-1445.
[34]Mayo LD, Dixon JE, Durden DL, et al. PTEN protects p53 from Mdm2 and sensitizes cancer cells to chemotherapy. J Bio Chem, 2002, 277(7):5484-5489.
[35]Huang H, Cheville JC, Pan Y, et al. PTEN induces chemosensitivity in PTEN-mutated prostate cancer cells by suppression of Bcl-2 expression. J Biol Chem, 2001, 276(42): 38830 -38836.
[36]Yuan XJ, Whang YE. PTEN sensilizes prostate cancer cells to death receptor mediated and drug induced apoptosis through a FADD dependent pathway . Oncogene, 2002, 21(2): 319 -327.
[37]Tanaka M, Koul D, Davies MA, et al. MMAC1/PTEN inhibits cell growth and induces chemosensitivity to doxorubicin in human bladder cancer cells. Onco gene, 2000, 19(47):5406 - 5412.
[38] Anai S, Goodison S, Shiverick K, et al. Combination of PTEN gene therapy andradiation inhibits the growth of human prostate cancer xenografts. Hum Gene Ther, 2006, 17(10):975- 984.
[39] Huang H, Cheville JC, Pan Y, et al. PTEN induces chemosensitivity in PTEN-mutated prostate cancer cells by suppression of Bcl-2 expression. J Biol Chem, 2001, 276(42): 38830- 38836.
[41] Gomes CP, Andrade LA. PTEN and p53 expression in primary ovarian carcinomas: immunohistochemical study and discussion of pathogenetic mechanisms. Int J Gynecol Cancer, 2006, 16(1):254- 258.
[42]常明章,孙彦,周剑勇. PTEN在喉癌及癌旁组织中的表达及其临床意义.实用临床医学,2006, 7(6):13-16.
[43]白伟良,任重,李国栋. PTEN基因在喉鳞癌中的表达及意义.中国医科大学学报, 2005,(6):238-239.
[44]吴先光,何淑华,沈志等.喉癌组织中抑癌基因PTEN的表达及意义.中国中西医结合耳鼻咽喉科杂志, 2005, 13(4):186-188.
[45]常傲霜,田禾,陈干美等.抑癌因子PTEN在喉鳞癌组织中的表达.贵阳医学院学报, 2006,31(2):98-100.
[46]吴强,庄坤,姚宪义,等. p53和PTEN的表达与喉癌颈淋巴结转移的相关性研究.哈尔滨医科大学学报,2006, 40(2):135-137.
[47] Seki M, Iwakawa J, Cheng H, et al. p53 and PTEN/MMAC1/TEP1 gene therapy of human prostate PC-3 carcinoma xenograft, using transferrin-facilitated lipofection gene delivery strategy. Hum Gene Ther, 2002, 13(6):761- 773.
[48] Rosser CJ, Tanaka M, Pisters LL, et al. Adenoviral-mediated PTEN transgene expression sensitizes Bcl-2-expressing prostate cancer cells to radiation. Cancer Gene Therapy, 2004, 11(4):273- 279.
[49] Tian XX, Zhang YG, Du J, et al. Effects of cotransfection of antisense-EGFR and wild-type PTEN cDNA on human glioblastoma cells. Neuropathology, 2006,26(3): 178- 187.
[50] Tanaka M, Grossman HB. In vivo gene therapy of human bladder cancer with PTEN suppresses tumor growth, downregulates phosphorylated Akt, and increases sensitivity to doxorubicin. Gene Ther, 2003, 10(19):1636- 1642.
[51] Konopka B, Janiec-Jankowska A, Czapczak D, et al. Molecular genetic defects in endometrial carcinomas: microsatellite instability, PTEN and betacatenin(CTNNB1) genes mutations. J Cancer Res Clin Oncol, 2007, 133(6): 361-371.
[52]辛丽红,李雅莉. PTEN基因与肿瘤研究进展.陕西医学杂志, 2005,34(5):594-595.
[53] Bakiewicz A, Gozdzik J, Spomy S. PTEN gene expression in the endometrial mucosa. Ginekol Pol, 2006, 77(4):323-329.
[1] Del Valle L, Enam S, Lassak A, et al. Insulin-like growth factor I receptor activity in human medulloblastomas. Clin Cancer Res, 2002,8(6):1822-1830.
[2] VellaV, Sciacca L, Pandini G et al. The IGF system in thyroid cancer: new concepts. Mol Pathol. 2001, 54(3):121-124.
[3] Weber MM, Fottner C, Wolf E. The role of the insulin-like growth factor system in adrenocortical tumourigenesis. Eur J Clin Invest, 2000, 30 Suppl 3:69-75.
[4] Sachdev D, Li SL, Hartell JS, et al. A chimeric humanized single-chain antibody against the type I insulin-like growth factor ( IGF) receptor renders breast cancer cells refractory to the mitogenic effects of IGF-I. Cancer Res, 2003, 63(3):627-635.
[5] Resnicoff M. Antitumors effects elicited by antisense mediated down regulation of the insulin like growth factorI receptor. Int J Mol Med, 1998,l(5):883-888.
[6]王瑶,委阁. IGF-1R在宫颈癌和淋巴结转移组织中表达的临床意义.现代妇产科进展, 2007,16(2): 103-105.
[7]方宏才,李威.胰岛素样生长因子1受体和肿瘤的关系.广东医学, 2007,28(9):1530-1532.
[8]武广彬,黄昌明.胰岛素样生长因子1型受体肿瘤靶向治疗.国际肿瘤学杂志,2006,33(4):253-256.
[9]曾翔,张唯力. IGF家族和前列腺增生的研究进展.中国男科学杂志, 2007,21(10):65-67.
[10] Tanaka Y, Kobayashi H, Suzuki M, et al. Genetic downregulation of pregnancy associated plasma protein-A (PAPP-A) by bikunin reduces IGF-I-dependent Akt and Erk1/2 activation and subsequently reduces ovarian cancer cell growth,invasion and metastasis. Int J Cancer, 2004, 109(3): 336-347.
[11] Remacle-Bonnet M, Garrouste F, Baillat G, et al. Membrane rafts segregate pro-from anti-apoptotic insulin-like growth factor-Ⅰreceptor signaling in colon carcinoma cells stimulated by members of the tumor necrosis factor superfamily. Am J Pathol, 2005, 167(3): 761-773.
[12]何振宇,管迅行. IGF-1R表达与乳腺癌细胞放射抗拒的相关性.中华实用医学, 2004, 6(13): 44-46.
[13]陈照丽,王欣,黄秉仁. IGF系统的生物学功能与其与肿瘤的关系.国外医学分子生物学分册, 2003, 25(1): 34-37.
[14] Li L, Yu H, Schumacher F, et al. Relation of serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 to risk of prostate cancer (United States).Cancer Causes Control, 2003,14(8): 721-726.
[15] Dupont J, LeRoith D. Insulin and insulin-like growth factor I receptors: similarities and differences in signal transduction. Horm Res, 2001, 55(Suppl 2): 22-26.
[16] Samani AA, Brodt P. The receptor for the type 1 insulin-like growth factor and its ligands regulate multiple cellular functions that impact on metastasis. Surg Oncol Clin N Am, 2001, 10(2):289-312.
[17]李鹏胜,彭俊生,肖方联.胃癌及其转移淋巴结组织中胰岛素样生长因子-I的表达及其临床意义.实用癌症杂志, 2006,21(6):579-581.
[18] Jiang Y, Wang L, Gong W, et al. A high expression level of insulin-like growth factor I receptor is associated with increased expression of transcription factor Sp1 and regional lymph node metastasis of human gastric cancer. Clin Exp Metastasis, 2004, 21(8):755-764.
[19] Peiro G, Lohse P, Mayr D, et al. Insulin-like growth factor-I receptor and PTEN protein expression in endometrial carcinoma. Correlation with bax and bcl-2expression, microsatellite instability status, and outcome. Am J Clin Pathol, 2003, 120(1): 78-85.
[20] Piestrzeniewicz-Ulanska D, Brys M, Semczuk A, et al. TGF-βsignaling is disrupted in endometrial-type endometrial cancinomas. Gynecologic oncology, 2004, 95(1):173-180.
[21] Lukanova A, Lundin E, Toniolo P, et al. Circulating levels of insulin-like growth factor-1 and risk of ovarian cancer. INt.J.cancer, 2002, 101(6): 549-554
[22] Min Y, AdachiY, Yamamoto H, et al. Insulin-like growth factor I receptor blockade enhances chemotherapy and radiation responses and inhibits tumour growth in human gastric cancer xenografts. Gut, 2005, 54(5): 591-600.
[23] Shen MR,Hsu YM,Hsu KF,et al. Insulin-like growth factor 1 is a potent stimulator Of cervical cancer cell invasiveness and proliferation that is modulated by aανβ3 integrin signaling. Carcinogenesis, 2006, 27(5): 962-971
[24]Pavelic K, Bukovie D, Pavelic J. The role insulin-like growth factor 2 and its receptor in human tumors. Mol Med, 2002, 8(12):771-780
[25]Maloney EK, Mclaughlin JL, Dagdigian NE, et al. An anti-insulin-like growth factor I receptor antibody that is a potent inhibitor of cancer cell proliferation. Caneer Res, 2003, 63(16):5073-5083
[26]牛朝诗,傅先明,汪业汉,等.多聚凝胶介导IGF-IR反义寡核苷酸治疗体内胶质瘤的实验研究.中华神经外科杂志, 2004,20(5):357-361.
[27] Burtrum D, Zhu ZP, Lu D, et al. A fully human monoclonal to the Insulin-like growth factor I receptor blocks ligand-dependent signaling and inhibits huaman tumor growth in vivo. Cancer research, 2003, 63(24): 8912-8921
[28] Andrews DW, Resnicoff M, Flanders AE,et al. Results of a pilot study involving the use of an antisense oligodeoxynucleotide directed against the insulin-like growth factor type I receptor in malignant astrocytomas. J Clin Oncol, 2001, 19(8): 2189 -2200.
[29] Benini S, Manara MC, Baldini N, et al. Inhibition of insulin-like growth factor I receptor increases the antitumor activity of doxorubicin and vincristine against Ewing’s sarcoma cells. Clin Cancer Res, 2001, 7 (6): 1790 -1797.
[30] Blum G, Gazit A, Levitzki A. Development of new IGF-1 receptor kinase inhibitors using catechol mimics . JBiol Chem, 2003, 278 (42):40442-40454.
[31]Tang Y, Zhang D, Fallavollita L, et al. Vascular endothelial growth factor C expression and lymph node metastasis are regulated by the type I insulin-like growth factor receptor. Cancer Research, 2003, 63(6):1166-1171.
[32]Sun HZ , Wu SF , Tu ZH. Knockdown of IGF-IR by Antisense Oligodeoxynucleotide auguments the sensitivity of bladder cancer cells to Mitomycin. Acta Pharmacol Sin 2001, 22(9): 841-846.
[33] Camirand A, Lu Y, Pollak M. Co targeting HER2/ErbB2 and insulin-like growth factor-1 receptors causes synergistic inhibition of growth in HER2 overexpressing breast cancer cells. Med Sci Monit, 2002, 8(12): BR521-526.
[34]季晨阳,刘来显,罗荣成,等.乳腺癌组织中胰岛素样生长因子1型受体的表达与病理学变化及预后的关系.中国临床康复, 2004,8:8003-8006.
[35]迟小岩,王言奎.子宫内膜癌组织IGF-1与其受体表达及意义.齐鲁医学杂志, 2008,23(3):198-203.
[36]车娜,葛荣明,陈玮伦. IGF-1、IGF-1R在喉鳞癌中的表达及意义.同济大学学报(医学版) , 2007 ,28(6):17-21.
[37] DuPont J, Le Roith D. Insulin-like growth factor I and oestradiol promote cell proliferation of MCF-7 breast cancer cells: new insights into their synergistic effects. Mol Pathol. 2001, 54(3):149 154.