宫颈鳞癌组织芯片中TSLC1和E-cad的表达及相关性研究
|
摘要
目的:探讨肺癌肿瘤阻抑基因-1(TSLC1)、上皮型钙粘蛋白(E-cadherin,E-cad)在宫颈鳞癌组织芯片中的表达及其临床意义,并分析两者的相关性。
方法:应用组织芯片、免疫组织化学法(SP法)和图像分析技术对29例宫颈鳞癌组织、20例宫颈上皮内瘤变、10例正常宫颈组织TSLC1、E-cad蛋白含量进行研究。
结果:TSLC1、E-cad在正常宫颈及CINⅠ级组织中,多呈强阳性表达,CINⅡ级以上及宫颈鳞癌组织表达呈递减趋势,差异有统计学意义(P<0.05)。宫颈鳞癌组织中TSLC1蛋白表达失活与淋巴转移有关(t=4.558,P=0.000);与组织病理分级无关(P>0.05)。E-cad蛋白表达失活与组织病理学分级和淋巴转移有关(P<0.05)。TSLC1蛋白、E-cad蛋白表达呈正相关(r_s=0.678,P=0.000)。
结论:组织芯片是大规模平行检测多基因蛋白表达的一种方法;TSLC1、E-cad蛋白表达失活使其丧失了抑癌作用,促使正常宫颈上皮细胞癌变的一个重要因素。
Objective:To detect the expression of TSLC1 and E-cadherin in cervical cancer by tissue micro array and to evaluate their clinical significance and correlation between the two genes.
Methods:59 specimens of tissues,including squamous carcinoma of the cervix,CINs and normal tissues underwent micro array examination and immunohistochenmistry to detect the expression of TSLC1 and E-cadherin.The intensity of TSLC1 and E-cadherin protein were investigated by analyzing with imaging technique.
Results:The result showed that the expression of strong positive cell in normal cervical tissue and CINⅠwere significant higher than those of CINⅡ,CINⅢand squamous carcinoma of the cervix(P＜0.05).There was no association between TSLC1 expression and histological type(P＞0.05).But the expression of TSLC1 was significantly correlated with lymphatic metastasis(t =4.558,P =0.000).Inactivation of E-cadherin gene expression in cervical cancer was significantly related to do with lymphatic metastasis and histological type(P＜0.05).The expression of TSLC1 and E-cadherin in cervical tissue were positive correlation(r=0.678,P=0.000).
Conclusion:Tissue microarray technique is effective method to detect multiple gene protein expression.Inactivation of TSLC1 and E-cadherin gene expression is an important factor in the uterine cervical carcinogenesis.
方法:应用组织芯片、免疫组织化学法(SP法)和图像分析技术对29例宫颈鳞癌组织、20例宫颈上皮内瘤变、10例正常宫颈组织TSLC1、E-cad蛋白含量进行研究。
结果:TSLC1、E-cad在正常宫颈及CINⅠ级组织中,多呈强阳性表达,CINⅡ级以上及宫颈鳞癌组织表达呈递减趋势,差异有统计学意义(P<0.05)。宫颈鳞癌组织中TSLC1蛋白表达失活与淋巴转移有关(t=4.558,P=0.000);与组织病理分级无关(P>0.05)。E-cad蛋白表达失活与组织病理学分级和淋巴转移有关(P<0.05)。TSLC1蛋白、E-cad蛋白表达呈正相关(r_s=0.678,P=0.000)。
结论:组织芯片是大规模平行检测多基因蛋白表达的一种方法;TSLC1、E-cad蛋白表达失活使其丧失了抑癌作用,促使正常宫颈上皮细胞癌变的一个重要因素。
Objective:To detect the expression of TSLC1 and E-cadherin in cervical cancer by tissue micro array and to evaluate their clinical significance and correlation between the two genes.
Methods:59 specimens of tissues,including squamous carcinoma of the cervix,CINs and normal tissues underwent micro array examination and immunohistochenmistry to detect the expression of TSLC1 and E-cadherin.The intensity of TSLC1 and E-cadherin protein were investigated by analyzing with imaging technique.
Results:The result showed that the expression of strong positive cell in normal cervical tissue and CINⅠwere significant higher than those of CINⅡ,CINⅢand squamous carcinoma of the cervix(P＜0.05).There was no association between TSLC1 expression and histological type(P＞0.05).But the expression of TSLC1 was significantly correlated with lymphatic metastasis(t =4.558,P =0.000).Inactivation of E-cadherin gene expression in cervical cancer was significantly related to do with lymphatic metastasis and histological type(P＜0.05).The expression of TSLC1 and E-cadherin in cervical tissue were positive correlation(r=0.678,P=0.000).
Conclusion:Tissue microarray technique is effective method to detect multiple gene protein expression.Inactivation of TSLC1 and E-cadherin gene expression is an important factor in the uterine cervical carcinogenesis.
引文
[1] ParkinDM,BrayF,FerlayJ,et al.Estimating the world cancer burden:Globocan 2000[J].Int J Cancer,2001,94:153-156.
[2] McLachlin CM. Human papillomavirus in cervical neoplasia.Role,risk factors,and implications[J].Clin Lab Med,2000,20(2):257-270.
[3] Kleihus P,Ohgaki H,Phenotype vs genotype in the evolution of astrocytic brain tumors[J].Toxicol Pathol,2000,28:164-170.
[4] Guan JL. Shalloway D. Regulation of focal adhesionAssociated protein tymsine kinase by both cellular adhesion and oneogenie transformation[J] .Nature, 1992,358(2):690-692.
[5] Akihiko Ito,Morihito Okada,Kazuya Uchino,et al.Expression of the TSLC1 adhe sion molecule in pulmonary epithelium and its down-regulation in pulmonary adenocarcinoma other than bronchioloalveolar carcinoma[J].Lab Invest,2003,83:1175-1183.
[6] Pletcher MT,Nobukuni T,Fukuhara H,et al.Identification of tumor suppressor candidate genes by physical and sequence mapping of the TSLC1 region of human chromosome 11q23[J].Gene,2001,273:181-189.
[7] Tatsushi Shingai,Wataru Ikeda,Shigeki Kakunaga,et al.Nectin-like molecule-2/ IGSF4/RA175/SgIGSF/TSLC1/SynCAM1 in cell-cell adhesion and transmem-brane protein localization in epithelial cells[J].Biol Chem,2003,278:35421-3542.
[8] Masuda M,Yageta M,Fukuhara H,et al.The tumor suppressor protein TSLC1 is involved in cell-cell adhesion[J].Biol Chem,2002,277(34):31014-31019.
[9] Fujita E,Soyama A,Momoi T,et al.RA175,which is the mouse ortholog of TSLC1,a tumor suppressor gene in human lung cancer, is a cell adhesion mole-cule[J].Exp Cell Res,2003,287(1):57.
[10] Yamada D,Yoshida M, Williams YN,et al.Disruption of spermatogenic cell adhesion and male infertility in mice lacking TSLC1/IGSF4,an immunoglobulin super family cell adhesion molecule[J].Mol Cell Biol,2006,26(9):3610-3624.
[11] Boles KS,Barchet W,Diacovo T,Cella M,et al.The tumor suppressor TSLC1/ NECL-2triggers NK-cell and CD8+T-cell responses through the cell-surface receptor CRTAM[J].Biol Chem,2005,106(3):779-786.
[12] Galibert L,Diemer GS,Liu Z,et al.Nectij-like protein 2 defines a subset of T-cell zone dendritic cells and is a ligand for class-1 -restricted T-cell-associated molecule[J].BiolChem,2005,280(23):21955-21964.
[13] Uchino K,Ito A,Wakayama T,Koma Y,et al.Clinical implication and prognostic significance of the tumor suppressor TSLC1 gene detected in adenocarcinoma of the lung.[J]Cancer, 2003,98(5).1002-1007.
[14] Surace EI,Lusis E,Murakami Y,et al.Loss of tumor suppressor in lung cancer-1 (TSLC1) expression in meningioma correlates with increased malignancy grade and reduced patient survival[J].Neuropathol Exp Neurol,2004,63(10): 1015—1027.
[15] Ito A,Okada M,Uchino K,et al.Expression of the TSLC1 adhesion molecule in pulmonary epithelium and its down-regulation in pulmonary adenocarcinoma other than bronchioalveolar carcinoma[J].Lab Invest,2003,83(8): 1175-1183.
[16] Goto A,Niki T,Chi-Pin L,et al.Loss of TSLC1 expression in lung denocarcinoma:a relationships with histological subtypes, sex and prognostic significance[J].Cancer Sci,2005,96(8):480-486.
[17] Sasaki H, Nishikata I,Shiraga T,et al.Overexpression of a cell adhesion molecule ,TSLC1,as a possible molecular marker for acute-type adult T-cell leukemia[J].Blood,2005,105(3):1204-1213.
[18] Mao X,Seidlitz E,ruant R,Hitt M,et al.Re-expression of TSLC1 in a non-small-cell lung cancer cell line induce apoptosis and inhibits tumor growth[J].Ncogene ,2004,23(33):5632-5642.
[19] Sussan TE,Pletcher MT,Murakami Y,Reeves RH,et al.Tumor suppressor in lung cancer 1 alters tumorigenic growth properties and gene expression[J].Mol Cancer,2005,5(4):28.
[20] Masuda M,Kikuchi S,Maruyama T,Sakurai-Yageta M,et al.Tumor suppressor in lung cancer 1 suppresses epithelial cell scattering and tubulogenesis.[J]Biol Chem,2005,280(51): 42164-42171.
[21] Kikuchi S,Yamada D,Fukami T,et al.Hypermethylation of the TSLC1/IGSF4 promoter is associated with tobacco smoking and a poor prognosis in primary nonsmall cell lung carcinoma[J].Cancer,2006,106(8):1751-1758.
[22] Fukami T,Fukuhara H,Kuramochi M,et al.Promoter methylation of the TSLC1 gene in advanced lung tumors and various cancer cell lines[J].Int J Cancer, 2003,107(1):53-59.
[23] Allinen M,Peri L,Kujala S,et al.Analysis of 11q21-24 loss of heterozygosity candidate target genes in breast cancer: indications of TSLC1 promoter hyper methylation[J].Genes Chromosomes Cancer,2002,34(4):384-389.
[24] Jansen M,Fukushima N,Rosty C,et al. Aberrant methylation of the 5' CpG island of TSLC1 is common in pancreatic ductal adenocarcinoma and is first manifest in high-grade PanlNs[J].Cancer Biol Ther,2002,(3):297-299.
[25] Steenbergen RD,Kramer D, Braakhuis BJ,et al.TSLCl gene silencing in cervical cancer cell lines and cervical neoplasia[J].Natl Cancer Inst,2004,96:294-305.
[26] Teiichiro Honda,Gen Tamura,Takayoshi Waki,et al.Hypermethylation of the TSLC1 gene promoter in primary gastric cancers and gastric cancer cell lines[J]. Cancer Res,2002,93.857-860.
[27] Hiroshi Fukuhara,Masami Kuramochi,Takeshi Fukami, et al.Promoter methylation of TSLC1 and tumor suppression by its gene product in human prostate cancer[J]. Cancer Res,2002,93:605-609.
[28] Jawhari A,Jordan P,Mentele E,et al.Abnormal immunoreactivity of the E-cad-atenin complex in gastric carcinoma;relationship with patients' survival[J]. Gastroen-terology, 1997,112,46-54.
[29] Bukholm IK,Nesland JM,Karesen R,et al.E-cadherin and alpha-,beta-,and gamma-catenin protein expression in relation to metastasis in human breast carcinoma[J].Pathol,1998,185(3):262-266.
[30] Brabletz T,Jung A,Dag S,et al.Beta-Catenin induces invasive growth by activating matrix metalloproteinases in colorectal carcinoma[J].Verh Dtsch Ges Pathol,2000,84:175-181.
[31] Hecht A,Kemler R,et al.Curbing the nuclear activities of beta-catenin,control over Wnt target gene expression[J].EMBO Rep,2000,1(1):24-28.
[32] Stockinger A,Eger A,Wolf J,et al.E-cadherin regulates cell growth by modulating proliferation -dependent beta-catenin transcriptional activity[J].Cell Biol,2001, 154(6):1185-1196.
[33] Gottardi CJ,Gumbiner BM,et al. Adhesion signaling: how beta-catenin interacts with its partners[J].Curr Biol,2001,11(19): 792-794.
[34] Miyaki M,Iijima T,Kimura J,et al.Frequent mutation of beta-catenin and APC genes in primary colorectal tumors from patients with hereditary nonpolyposis colorectal cance r[J].Cancer Res,1999,59(18):4506-4509.
[35] Persad S,Troussard Aa,Mcphee TR,et al.Tumor suppressor PTEN inhibits nuclear accumulation of beta-catenin and T cell/lymphoid enhancer factor 1-mediated transcriptional activation[J].Cell Biol,2001,153(6):1161-1174.
[36] Jose Piedra,Daniel Martínez,Julio Castano,et al.Regulation of β-Catenin structure and activety by tyrosine phosphorylation[J].Biol Chem,2001,276:20436-20443.
[37] Katayama M,Hirai S,Kamihagi N,et al. Soluble E-cadherin fragments increased in circulation of cancer pqtients[J].Br J Cancer,1994,69:580.
[38] Behrens J,Jerchow BA,Wurtele M,et al.Functional interaction of an axin homo-log, conductin, with beta-catenin, APC,and GSK3beta[J]. Science, 1998,24,280 (5363):596-599.
[39] Eidelman S,Caroline H.Expression of the cell-cell adhesion glycoprotein cell-Cam 120/80 in normal human tissue and tumors[J].Am J Pathol, 1989,135:101 -110.
[40] Guriec N ,Marcellin L,Gairard B,et al.E-cadherin mRNA expression in breast carcinoma correlate with overall and discase free survival[J].Lavasion metastasis, 1996,16:19-26.
[41] BerX G,Cleton AM,Strumane,et al.E-cadherin is in a majority of invasive human lobubar breast cancers by truncation mutatives throughant its extracelluar domain[J].Oncogene,1996,13(9):1919-1925.
[42] Ong A maines-bandior SL,Roskelley CD,et al. An ovarian adenocarcinoma line derived from SV40/E-cadherin transfected normal human ovarian surface epithelium [J].Int J Cancer,2000,85(3):430-437.
[43] Behrens J,Von kries JP,Kohi M,et al.Functional interaction of catenin with the transcription factor LET-1[J].Nature,1996,382:638-642.
[44] Fruhwald MC,Plass C.Global and gene-specific methylation patterns in cancer.Aspects of tumor biology and clinical potential[J].Mol Genet Metab,2002,75 (1):1-16.
[45] Nojima D,Nakajima K,Li L C,et al.CPG methylation of promoter region inactivates E-cad gene in renal cell carcinoma[J].Mol Carcinog,2001,32(1): 19-27.
[46] Kwon GY,Yoo BC,Koh KC,et al.Promoter methylation of E-cadherin in hepato cellular carcinomas and dysplastic nodules[J].Korean Med Sci,2005,20(2):242-247.
[47] Chen CL,Liu SS,Ip SM,et al.E-cadherin expression is silenced by DNA methylation in cervical cancer cell lines and tumors[J].Eur J Cancer,2003,39(4):517-523.
[48] Kang S,Kim JW,Kang GH,et al.Polymorphism in folate-and-methionine-meta-bolizing enzyme and aberrant CpG island hypermethylation in uterine cervical cancer[J].Gynecol Oncol,2005,96(1): 173-180.
[49] Narayan G, Arias-pulido H,Koul S,et al.Frequent promoter methylation of CDH1 ,DAPK,RARB,and HIClgenes in carcinoma of cervix uteri:its relationship to clinical outcome[J].Mol Cancer,2003,2(1):24-35.
[50] Sakajiri S,Kumagai T,Kawamata N,et al.Histone deacetylase inhibitors profoundly decrease proliferation of human lymphoid cancer cell lines[J].Exp Hematol,2005,33(1):53-61.
[51] Saito T, Nishimura M,Yamasaki H,et al.Hypermethylation in promoter region of E-cadherin gene is associated with tumor dedifferention and myometrial invasion in endometrial carcinoma[J].Cancer,2003,97(4): 1002-1009.
[52] Nishimura M, Saito T, Yamasaki H,et al. Suppression of gap junctional intercellu-larcommunication via 5'CpG island methylation in promoter region of E-cad gene in endometrial cancer cells[J].Carcinogenesis,2003,24(10): 1615-1623.
[53]Rathi A,Virmani AK,Schorge JO,et al,Methylation profiles of sporadic ovarian tumors and nonmalignant ovaries from high-risk women[J].Clin Cancer Res,2002,8(11):3324-3331.
[54]Makarla PB,Saboorian MH,Ashfaq R,et al.Promoter hypermethylation profile of ovarian epithelial neoplasms[J].Clin Cancer Res,2005,11(15):5365-5369.
[55]Getsios S,MacCalman CD.Cadherin-11 modulates the terminal differentiation and fusion of human trophoblastic cell in vitro[J].Dev Biol,2003,257(1):41-54.
[56]Bischof P,Meisser A,Campana A,et al.Mechanisms of endometrial control of trophoblast invasion[J].Reprod Fertil Suppl,2000,55(1):65-71.
[57]Masuda M,Yageta M,Fukuhara Hetal,et al.The tumor suppressor protein TSLC1is involved in cell-cell adhesion[J].J Biol Chem,2002,277(34):31014-31019.
[58]饶晓松,刘翠苓,李敏等.TSLC1和BLU基因在鼻NK/T细胞淋巴瘤众CpG岛甲基化研究[J].肿瘤研究与临床,2006,18(8):534-537.
[59]王军利,张惠中,白万胜等.喉癌组织中TSLC1基因启动子过甲基化及mRNA 表达[J].第四军医大学学报,2007,28(7):651-653.
[60]Ohta Y,Itoh K,Yaoi T,et al.Spatiotemporal patterns of expression of IGSF4 in developing mouse nervous system[J].Brain Res Dev Brain Res,2005,156:23-31.
[61]Houshmandi SS,Surace EI,Zhang HB,et al.Tumor suppressor in lung cancer-1(TSLC1)functions as a glioma tumor suppressor[J].2006,28,67(10):1863-1866.
[62]Birchmeier W,Behrens J.Cadherin expression in carcinomas:role in the formation of cell junction and the prevention of invasiveness[J].Biochim Biophys Acta ,1994,1198:11-26.
[63]Liu TJ,Yuan WQ.Expression of cyclinD1 p53 E-cadherin and its significance in intracpitheliol neoplasia and carcinoma of stomach[J].Chinese Joumal of Clinical Oncology,2004,31(22):1307-1308.
[64]Charalabopoulos K,Gogali A,Kostoula OK,et al.Caherin superfamily of adhesion molecules in primary lung cancer.Exp Oncol,2004,26(4):256-260.
[65]Pecina-Slaus N.Tumor suppressor gene E-cadherin and its role in normal and malignant cells.Cancer Cell Int,2003,3(1):17.
[2] McLachlin CM. Human papillomavirus in cervical neoplasia.Role,risk factors,and implications[J].Clin Lab Med,2000,20(2):257-270.
[3] Kleihus P,Ohgaki H,Phenotype vs genotype in the evolution of astrocytic brain tumors[J].Toxicol Pathol,2000,28:164-170.
[4] Guan JL. Shalloway D. Regulation of focal adhesionAssociated protein tymsine kinase by both cellular adhesion and oneogenie transformation[J] .Nature, 1992,358(2):690-692.
[5] Akihiko Ito,Morihito Okada,Kazuya Uchino,et al.Expression of the TSLC1 adhe sion molecule in pulmonary epithelium and its down-regulation in pulmonary adenocarcinoma other than bronchioloalveolar carcinoma[J].Lab Invest,2003,83:1175-1183.
[6] Pletcher MT,Nobukuni T,Fukuhara H,et al.Identification of tumor suppressor candidate genes by physical and sequence mapping of the TSLC1 region of human chromosome 11q23[J].Gene,2001,273:181-189.
[7] Tatsushi Shingai,Wataru Ikeda,Shigeki Kakunaga,et al.Nectin-like molecule-2/ IGSF4/RA175/SgIGSF/TSLC1/SynCAM1 in cell-cell adhesion and transmem-brane protein localization in epithelial cells[J].Biol Chem,2003,278:35421-3542.
[8] Masuda M,Yageta M,Fukuhara H,et al.The tumor suppressor protein TSLC1 is involved in cell-cell adhesion[J].Biol Chem,2002,277(34):31014-31019.
[9] Fujita E,Soyama A,Momoi T,et al.RA175,which is the mouse ortholog of TSLC1,a tumor suppressor gene in human lung cancer, is a cell adhesion mole-cule[J].Exp Cell Res,2003,287(1):57.
[10] Yamada D,Yoshida M, Williams YN,et al.Disruption of spermatogenic cell adhesion and male infertility in mice lacking TSLC1/IGSF4,an immunoglobulin super family cell adhesion molecule[J].Mol Cell Biol,2006,26(9):3610-3624.
[11] Boles KS,Barchet W,Diacovo T,Cella M,et al.The tumor suppressor TSLC1/ NECL-2triggers NK-cell and CD8+T-cell responses through the cell-surface receptor CRTAM[J].Biol Chem,2005,106(3):779-786.
[12] Galibert L,Diemer GS,Liu Z,et al.Nectij-like protein 2 defines a subset of T-cell zone dendritic cells and is a ligand for class-1 -restricted T-cell-associated molecule[J].BiolChem,2005,280(23):21955-21964.
[13] Uchino K,Ito A,Wakayama T,Koma Y,et al.Clinical implication and prognostic significance of the tumor suppressor TSLC1 gene detected in adenocarcinoma of the lung.[J]Cancer, 2003,98(5).1002-1007.
[14] Surace EI,Lusis E,Murakami Y,et al.Loss of tumor suppressor in lung cancer-1 (TSLC1) expression in meningioma correlates with increased malignancy grade and reduced patient survival[J].Neuropathol Exp Neurol,2004,63(10): 1015—1027.
[15] Ito A,Okada M,Uchino K,et al.Expression of the TSLC1 adhesion molecule in pulmonary epithelium and its down-regulation in pulmonary adenocarcinoma other than bronchioalveolar carcinoma[J].Lab Invest,2003,83(8): 1175-1183.
[16] Goto A,Niki T,Chi-Pin L,et al.Loss of TSLC1 expression in lung denocarcinoma:a relationships with histological subtypes, sex and prognostic significance[J].Cancer Sci,2005,96(8):480-486.
[17] Sasaki H, Nishikata I,Shiraga T,et al.Overexpression of a cell adhesion molecule ,TSLC1,as a possible molecular marker for acute-type adult T-cell leukemia[J].Blood,2005,105(3):1204-1213.
[18] Mao X,Seidlitz E,ruant R,Hitt M,et al.Re-expression of TSLC1 in a non-small-cell lung cancer cell line induce apoptosis and inhibits tumor growth[J].Ncogene ,2004,23(33):5632-5642.
[19] Sussan TE,Pletcher MT,Murakami Y,Reeves RH,et al.Tumor suppressor in lung cancer 1 alters tumorigenic growth properties and gene expression[J].Mol Cancer,2005,5(4):28.
[20] Masuda M,Kikuchi S,Maruyama T,Sakurai-Yageta M,et al.Tumor suppressor in lung cancer 1 suppresses epithelial cell scattering and tubulogenesis.[J]Biol Chem,2005,280(51): 42164-42171.
[21] Kikuchi S,Yamada D,Fukami T,et al.Hypermethylation of the TSLC1/IGSF4 promoter is associated with tobacco smoking and a poor prognosis in primary nonsmall cell lung carcinoma[J].Cancer,2006,106(8):1751-1758.
[22] Fukami T,Fukuhara H,Kuramochi M,et al.Promoter methylation of the TSLC1 gene in advanced lung tumors and various cancer cell lines[J].Int J Cancer, 2003,107(1):53-59.
[23] Allinen M,Peri L,Kujala S,et al.Analysis of 11q21-24 loss of heterozygosity candidate target genes in breast cancer: indications of TSLC1 promoter hyper methylation[J].Genes Chromosomes Cancer,2002,34(4):384-389.
[24] Jansen M,Fukushima N,Rosty C,et al. Aberrant methylation of the 5' CpG island of TSLC1 is common in pancreatic ductal adenocarcinoma and is first manifest in high-grade PanlNs[J].Cancer Biol Ther,2002,(3):297-299.
[25] Steenbergen RD,Kramer D, Braakhuis BJ,et al.TSLCl gene silencing in cervical cancer cell lines and cervical neoplasia[J].Natl Cancer Inst,2004,96:294-305.
[26] Teiichiro Honda,Gen Tamura,Takayoshi Waki,et al.Hypermethylation of the TSLC1 gene promoter in primary gastric cancers and gastric cancer cell lines[J]. Cancer Res,2002,93.857-860.
[27] Hiroshi Fukuhara,Masami Kuramochi,Takeshi Fukami, et al.Promoter methylation of TSLC1 and tumor suppression by its gene product in human prostate cancer[J]. Cancer Res,2002,93:605-609.
[28] Jawhari A,Jordan P,Mentele E,et al.Abnormal immunoreactivity of the E-cad-atenin complex in gastric carcinoma;relationship with patients' survival[J]. Gastroen-terology, 1997,112,46-54.
[29] Bukholm IK,Nesland JM,Karesen R,et al.E-cadherin and alpha-,beta-,and gamma-catenin protein expression in relation to metastasis in human breast carcinoma[J].Pathol,1998,185(3):262-266.
[30] Brabletz T,Jung A,Dag S,et al.Beta-Catenin induces invasive growth by activating matrix metalloproteinases in colorectal carcinoma[J].Verh Dtsch Ges Pathol,2000,84:175-181.
[31] Hecht A,Kemler R,et al.Curbing the nuclear activities of beta-catenin,control over Wnt target gene expression[J].EMBO Rep,2000,1(1):24-28.
[32] Stockinger A,Eger A,Wolf J,et al.E-cadherin regulates cell growth by modulating proliferation -dependent beta-catenin transcriptional activity[J].Cell Biol,2001, 154(6):1185-1196.
[33] Gottardi CJ,Gumbiner BM,et al. Adhesion signaling: how beta-catenin interacts with its partners[J].Curr Biol,2001,11(19): 792-794.
[34] Miyaki M,Iijima T,Kimura J,et al.Frequent mutation of beta-catenin and APC genes in primary colorectal tumors from patients with hereditary nonpolyposis colorectal cance r[J].Cancer Res,1999,59(18):4506-4509.
[35] Persad S,Troussard Aa,Mcphee TR,et al.Tumor suppressor PTEN inhibits nuclear accumulation of beta-catenin and T cell/lymphoid enhancer factor 1-mediated transcriptional activation[J].Cell Biol,2001,153(6):1161-1174.
[36] Jose Piedra,Daniel Martínez,Julio Castano,et al.Regulation of β-Catenin structure and activety by tyrosine phosphorylation[J].Biol Chem,2001,276:20436-20443.
[37] Katayama M,Hirai S,Kamihagi N,et al. Soluble E-cadherin fragments increased in circulation of cancer pqtients[J].Br J Cancer,1994,69:580.
[38] Behrens J,Jerchow BA,Wurtele M,et al.Functional interaction of an axin homo-log, conductin, with beta-catenin, APC,and GSK3beta[J]. Science, 1998,24,280 (5363):596-599.
[39] Eidelman S,Caroline H.Expression of the cell-cell adhesion glycoprotein cell-Cam 120/80 in normal human tissue and tumors[J].Am J Pathol, 1989,135:101 -110.
[40] Guriec N ,Marcellin L,Gairard B,et al.E-cadherin mRNA expression in breast carcinoma correlate with overall and discase free survival[J].Lavasion metastasis, 1996,16:19-26.
[41] BerX G,Cleton AM,Strumane,et al.E-cadherin is in a majority of invasive human lobubar breast cancers by truncation mutatives throughant its extracelluar domain[J].Oncogene,1996,13(9):1919-1925.
[42] Ong A maines-bandior SL,Roskelley CD,et al. An ovarian adenocarcinoma line derived from SV40/E-cadherin transfected normal human ovarian surface epithelium [J].Int J Cancer,2000,85(3):430-437.
[43] Behrens J,Von kries JP,Kohi M,et al.Functional interaction of catenin with the transcription factor LET-1[J].Nature,1996,382:638-642.
[44] Fruhwald MC,Plass C.Global and gene-specific methylation patterns in cancer.Aspects of tumor biology and clinical potential[J].Mol Genet Metab,2002,75 (1):1-16.
[45] Nojima D,Nakajima K,Li L C,et al.CPG methylation of promoter region inactivates E-cad gene in renal cell carcinoma[J].Mol Carcinog,2001,32(1): 19-27.
[46] Kwon GY,Yoo BC,Koh KC,et al.Promoter methylation of E-cadherin in hepato cellular carcinomas and dysplastic nodules[J].Korean Med Sci,2005,20(2):242-247.
[47] Chen CL,Liu SS,Ip SM,et al.E-cadherin expression is silenced by DNA methylation in cervical cancer cell lines and tumors[J].Eur J Cancer,2003,39(4):517-523.
[48] Kang S,Kim JW,Kang GH,et al.Polymorphism in folate-and-methionine-meta-bolizing enzyme and aberrant CpG island hypermethylation in uterine cervical cancer[J].Gynecol Oncol,2005,96(1): 173-180.
[49] Narayan G, Arias-pulido H,Koul S,et al.Frequent promoter methylation of CDH1 ,DAPK,RARB,and HIClgenes in carcinoma of cervix uteri:its relationship to clinical outcome[J].Mol Cancer,2003,2(1):24-35.
[50] Sakajiri S,Kumagai T,Kawamata N,et al.Histone deacetylase inhibitors profoundly decrease proliferation of human lymphoid cancer cell lines[J].Exp Hematol,2005,33(1):53-61.
[51] Saito T, Nishimura M,Yamasaki H,et al.Hypermethylation in promoter region of E-cadherin gene is associated with tumor dedifferention and myometrial invasion in endometrial carcinoma[J].Cancer,2003,97(4): 1002-1009.
[52] Nishimura M, Saito T, Yamasaki H,et al. Suppression of gap junctional intercellu-larcommunication via 5'CpG island methylation in promoter region of E-cad gene in endometrial cancer cells[J].Carcinogenesis,2003,24(10): 1615-1623.
[53]Rathi A,Virmani AK,Schorge JO,et al,Methylation profiles of sporadic ovarian tumors and nonmalignant ovaries from high-risk women[J].Clin Cancer Res,2002,8(11):3324-3331.
[54]Makarla PB,Saboorian MH,Ashfaq R,et al.Promoter hypermethylation profile of ovarian epithelial neoplasms[J].Clin Cancer Res,2005,11(15):5365-5369.
[55]Getsios S,MacCalman CD.Cadherin-11 modulates the terminal differentiation and fusion of human trophoblastic cell in vitro[J].Dev Biol,2003,257(1):41-54.
[56]Bischof P,Meisser A,Campana A,et al.Mechanisms of endometrial control of trophoblast invasion[J].Reprod Fertil Suppl,2000,55(1):65-71.
[57]Masuda M,Yageta M,Fukuhara Hetal,et al.The tumor suppressor protein TSLC1is involved in cell-cell adhesion[J].J Biol Chem,2002,277(34):31014-31019.
[58]饶晓松,刘翠苓,李敏等.TSLC1和BLU基因在鼻NK/T细胞淋巴瘤众CpG岛甲基化研究[J].肿瘤研究与临床,2006,18(8):534-537.
[59]王军利,张惠中,白万胜等.喉癌组织中TSLC1基因启动子过甲基化及mRNA 表达[J].第四军医大学学报,2007,28(7):651-653.
[60]Ohta Y,Itoh K,Yaoi T,et al.Spatiotemporal patterns of expression of IGSF4 in developing mouse nervous system[J].Brain Res Dev Brain Res,2005,156:23-31.
[61]Houshmandi SS,Surace EI,Zhang HB,et al.Tumor suppressor in lung cancer-1(TSLC1)functions as a glioma tumor suppressor[J].2006,28,67(10):1863-1866.
[62]Birchmeier W,Behrens J.Cadherin expression in carcinomas:role in the formation of cell junction and the prevention of invasiveness[J].Biochim Biophys Acta ,1994,1198:11-26.
[63]Liu TJ,Yuan WQ.Expression of cyclinD1 p53 E-cadherin and its significance in intracpitheliol neoplasia and carcinoma of stomach[J].Chinese Joumal of Clinical Oncology,2004,31(22):1307-1308.
[64]Charalabopoulos K,Gogali A,Kostoula OK,et al.Caherin superfamily of adhesion molecules in primary lung cancer.Exp Oncol,2004,26(4):256-260.
[65]Pecina-Slaus N.Tumor suppressor gene E-cadherin and its role in normal and malignant cells.Cancer Cell Int,2003,3(1):17.