CADM1与DAL-1/4.1B在大肠癌中的表达及临床意义
|
摘要
目的:研究CADM1和DAL-1/4.1B两种抑癌基因在大肠癌中的表达并分析两者之间及其与大肠癌各临床病理参数之间的关系,探讨CADM1和DAL-1/4.1B在大肠癌发生发展中的作用,为大肠癌的基因治疗提出新的思路。
方法:应用免疫组织化学(SABC法)检测30例大肠癌组织,10例大肠腺瘤组织,30例正常大肠组织中CADM1和DAL-1/4.1B两种抑癌基因的表达;应用Western-Blot法检测30例大肠癌组织,10例大肠腺瘤组织,30例正常大肠组织中CADM1及DAL-1/4.1B的表达,以图象分析软件进行半定量测定。
结果:大肠癌组织与大肠腺瘤组织、正常对照组织中CADM1和DAL-1/4.1B表达阳性率差异有统计学意义(23.33%/26.67%Vs70.00%/70.00%、23.33%/26.67%Vs 86.67%/83.33% P<0.05),Western-blot条带经图象分析软件测得大肠癌组织CADM1和DAL-1/4.1B吸光度与β-actin吸光度比值均显著低于大肠腺瘤、正常对照组织(0.229±0.053/0.223±0.052 Vs 0.299±0.068/0.291±0.066、0.229±0.053/0.223±0.052 Vs 0.418±0.081 /0.333±0.061, P<0.05)。CADM1和DAL-1/4.1B的表达部位和染色强度相似,半定量分析也显示两者呈正相关(r=0.710, P<0.05)。CADM1和DAL-1/4.1B的表达与大肠癌患者肿瘤分化程度、年龄、性别未见相关(P>0.05),而两者在Dukes分期C+D中的表达阳性率低于Dukes分期A+B差异有统计学意义(P<0.05)。
结论:大肠癌中CADMl和DAL-1/4.1B基因均呈现失活和蛋白表达下调,CADM1与DAL-1/4.1B通过相互作用共同发挥其肿瘤抑制作用并参与大肠癌的发生、发展。
Aims:To investigate the expression and clinicpathological significance of CADM1 and DAL-1/4.1B proteins in colorectal carcinoma,colorectal adenoma and normal colorectal mucosa specimens and its possible implications.
Methods: Immumohistochemical staining was performed to detect the expression of CADM1 and DAL-1/4.1B proteins in 30 cases of colorectal carcinoma tissues, 10 cases of colorectal adenoma tissues, and 30 cases of normal colorectal mucosa tissues.Western-blot was used to measure the protein expression of CADM1 and DAL-1/4.1B in 30 cases of colorectal cancer tissues, 10 cases of colorectal adenoma tissues, and 30 cases of normal colorectal mucosa tissues.Semi-determination was performed by image analysis software.
Results:The positive rate of CADM1 and DAL-1/4.1B showed downward trends in cancer tissues, colorectal adenoma tissues and normal control. Positive rate of CADM1 and DAL-1/4.1B was 23.33%/26.67% in cancer tissues, and 70%/70% in colorectal adenoma tissues, 86.67%/83.33% in normal control. The Western-blot band shows that the gray level of CADM1 and DAL-1/4.1B in cancer tissues is significantly lower than in colorectal adenoma tissues and normal control(0.229±0.053/0.223±0.052 Vs 0.299±0.068/0.291±0.066、0.229±0.053/0.223±0.052 Vs 0.418±0.081 /0.333±0.061, P<0.05). Expression and location of CADM1 protein were parallel and relevant with the expression of DAL-1/4.1B , the immunoreactive intensity of the two proteins was similar. Semiquantitative analysis showed that there was a positive correlation between the expression of CADM1 and DAL-1/4.1B(r=0.710, P<0.05). No relationship was found between expression of CADM1 and DAL-1/4.1B in age or histological differentiation and gender(P>0.05). But expression of CADM1 in Dukes stage C+D group was much lowher than Dukes stage A+B group (P<0.05).
Conclusions: Downregulation of CADM1 and DAL-1/4.1B proteins expression are exist in colorectal carcinoma. The inactivation of CADM1 and DAL-1/4.1B cause the growth and development of colorectal carcinoma. CADM1 and DAL-1/4.1B are interact with eachother through this progress.
方法:应用免疫组织化学(SABC法)检测30例大肠癌组织,10例大肠腺瘤组织,30例正常大肠组织中CADM1和DAL-1/4.1B两种抑癌基因的表达;应用Western-Blot法检测30例大肠癌组织,10例大肠腺瘤组织,30例正常大肠组织中CADM1及DAL-1/4.1B的表达,以图象分析软件进行半定量测定。
结果:大肠癌组织与大肠腺瘤组织、正常对照组织中CADM1和DAL-1/4.1B表达阳性率差异有统计学意义(23.33%/26.67%Vs70.00%/70.00%、23.33%/26.67%Vs 86.67%/83.33% P<0.05),Western-blot条带经图象分析软件测得大肠癌组织CADM1和DAL-1/4.1B吸光度与β-actin吸光度比值均显著低于大肠腺瘤、正常对照组织(0.229±0.053/0.223±0.052 Vs 0.299±0.068/0.291±0.066、0.229±0.053/0.223±0.052 Vs 0.418±0.081 /0.333±0.061, P<0.05)。CADM1和DAL-1/4.1B的表达部位和染色强度相似,半定量分析也显示两者呈正相关(r=0.710, P<0.05)。CADM1和DAL-1/4.1B的表达与大肠癌患者肿瘤分化程度、年龄、性别未见相关(P>0.05),而两者在Dukes分期C+D中的表达阳性率低于Dukes分期A+B差异有统计学意义(P<0.05)。
结论:大肠癌中CADMl和DAL-1/4.1B基因均呈现失活和蛋白表达下调,CADM1与DAL-1/4.1B通过相互作用共同发挥其肿瘤抑制作用并参与大肠癌的发生、发展。
Aims:To investigate the expression and clinicpathological significance of CADM1 and DAL-1/4.1B proteins in colorectal carcinoma,colorectal adenoma and normal colorectal mucosa specimens and its possible implications.
Methods: Immumohistochemical staining was performed to detect the expression of CADM1 and DAL-1/4.1B proteins in 30 cases of colorectal carcinoma tissues, 10 cases of colorectal adenoma tissues, and 30 cases of normal colorectal mucosa tissues.Western-blot was used to measure the protein expression of CADM1 and DAL-1/4.1B in 30 cases of colorectal cancer tissues, 10 cases of colorectal adenoma tissues, and 30 cases of normal colorectal mucosa tissues.Semi-determination was performed by image analysis software.
Results:The positive rate of CADM1 and DAL-1/4.1B showed downward trends in cancer tissues, colorectal adenoma tissues and normal control. Positive rate of CADM1 and DAL-1/4.1B was 23.33%/26.67% in cancer tissues, and 70%/70% in colorectal adenoma tissues, 86.67%/83.33% in normal control. The Western-blot band shows that the gray level of CADM1 and DAL-1/4.1B in cancer tissues is significantly lower than in colorectal adenoma tissues and normal control(0.229±0.053/0.223±0.052 Vs 0.299±0.068/0.291±0.066、0.229±0.053/0.223±0.052 Vs 0.418±0.081 /0.333±0.061, P<0.05). Expression and location of CADM1 protein were parallel and relevant with the expression of DAL-1/4.1B , the immunoreactive intensity of the two proteins was similar. Semiquantitative analysis showed that there was a positive correlation between the expression of CADM1 and DAL-1/4.1B(r=0.710, P<0.05). No relationship was found between expression of CADM1 and DAL-1/4.1B in age or histological differentiation and gender(P>0.05). But expression of CADM1 in Dukes stage C+D group was much lowher than Dukes stage A+B group (P<0.05).
Conclusions: Downregulation of CADM1 and DAL-1/4.1B proteins expression are exist in colorectal carcinoma. The inactivation of CADM1 and DAL-1/4.1B cause the growth and development of colorectal carcinoma. CADM1 and DAL-1/4.1B are interact with eachother through this progress.
引文
[1] Kuramochi M, Fukuhara H, Nobukuni T, et al.TSLC1 is a tumorsuppressor gene in human non-small-cell lung cancer. Nature Genetics, 2001;27(4):427-30.
[2] Tran YK, B?gler O, Gorse KM, et al.A novel member of the NF2/ERM/4.1 superfamily with growth suppressing properties in lung cancer. Cancer Res. 1999 Jan 1;59(1):35-43.
[3] Heller G, Geradts J, Ziegler B, et al.Downregulation of TSLC1 and DAL-1 expression occurs frequently in breast cancer. Breast Cancer Res Treat. 2007 Jul;103(3):283-91.
[4] Sakurai-Yageta M, Masuda M, Tsuboi Y, et al.Tumor suppressor CADM1 is involved in epithelial cell structure. Biochem Biophys Res Commun. 2009 Dec 18;390(3):977-82.
[5] Heller G, Fong KM, Girard L, et al.Expression and methylation pattern of TSLC1 cascade genes in lung carcinomas. Oncogene. 2006 Feb 9;25(6):959-68.
[6] Goto A, Niki T, Chi-Pin L, et al. Loss of TSLC1 expression in lung adenocarcinoma: relationships with histological subtypes, sex and prognostic significance. Cancer Sci. 2005 Aug;96(8):480-6.
[7] 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 hypermethylation.Genes Chromosomes Cancer. 2002 Aug;34(4):384-9.
[8] Bertolo C, Guerrero D, Vicente F, et al.Differences and molecular immunohistochemical parameters in the subtypes of infiltrating ductal breast cancer. Am J Clin Pathol. 2008 Sep;130(3):414-24.
[9] Houshmandi SS, Surace EI, Zhang HB, et al. Tumor suppressor in lung cancer-1 (TSLC1) functions as a glioma tumor suppressor. Neurology. 2006 Nov 28;67(10):1863-6.
[10] Fukami T, Fukuhara H, Kuramochi M, et al.Promoter methylation of the TSLC1 gene in advanced lung tumors and various cancer cell lines. Int J Cancer. 2003 Oct 20;107(1):53-9.
[11] Uchino K, Ito A, Wakayama T, et al.Clinical implication and prognostic significance of the tumor suppressor TSLC1 gene detected in adenocarcinoma of the lung. Cancer. 2003 Sep 1;98(5):1002-7.
[12] Kikuchi S, Yamada D, Fukami T, et al.Hypermethylation of the TSLC1/IGSF4promoter is associated with tobacco smoking and a poor prognosis in primary nonsmall cell lung carcinoma. Cancer. 2006 Apr 15;106(8):1751-8.
[13] Kitamura Y, Kurosawa G, Tanaka M, et al.Frequent overexpression of CADM1/IGSF4 in lung adenocarcinoma. Biochem Biophys Res Commun. 2009 Jun 12;383(4):480-4.
[14] Michels E, Hoebeeck J, De Preter K, et al.CADM1 is a strong neuroblastoma candidate gene that maps within a 3.72 Mb critical region of loss on 11q23. BMC Cancer. 2008 Jun 17;8:173.
[15] Nowacki S, Skowron M, Oberthuer A, et al.Expression of the tumour suppressor gene CADM1 is associated with favourable outcome and inhibits cell survival in neuroblastoma. Oncogene. 2008 May 22;27(23):3329-38.
[16] Fukuhara H, Kuramochi M, Fukami T, et al. Promoter methylation of TSLC1 and tumor suppression by its gene product in human prostate cancer. Jpn J Cancer Res. 2002 Jun;93(6):605-9.
[17] Williams YN, Masuda M, Sakurai-Yageta M, et al.Cell adhesion and prostate tumor-suppressor activity of TSLL2/IGSF4C, an immunoglobulin superfamily molecule homologous to TSLC1/IGSF4. Oncogene. 2006 Mar 9;25(10):1446-53.
[18] Murakami Y.Functional cloning of a tumor suppressor gene, TSLC1, in human non-small cell lung cancer. Oncogene. 2002 Oct 7;21(45):6936-48.
[19]Qin L, Zhu W, Xu T, et al.Effect of TSLC1 gene on proliferation, invasion and apoptosis of human hepatocellular carcinoma cell line HepG2. J Huazhong Univ Sci Technolog Med Sci. 2007 Oct;27(5):535-7.
[20] Honda T, Tamura G, Waki T, et al. Hypermethylation of the TSLC1 gene promoter in primary gastric cancers and gastric cancer cell lines. Jpn J Cancer Res. 2002 Aug;93(8):857-60.
[21] Lung HL, Cheng Y, Kumaran MK, et al. Fine mapping of the 11q22-23 tumor suppressive region and involvement of TSLC1 in nasopharyngeal carcinoma. Int J Cancer. 2004 Nov 20;112(4):628-35.
[22] Hui AB, Lo KW, Kwong J, et al. Epigenetic inactivation of TSLC1 gene in nasopharyngeal carcinoma. Mol Carcinog 2003; 38: 170–8.
[23] Ito T, Shimada Y, Hashimoto Y, et al. Involvement of TSLCI in progression ofesophageal squamous cell carcinoma. Cancer Res,2003,63(19):6320-6.
[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. Cancer Biol Ther 2002; 1: 293-6.
[25] Shimizu K, Onishi M, Sugata E, et al. Aberrant DNA methylation of the 5' upstream region of Tslc1 gene in hamster pancreatic tumors. Biochem Biophys Res Commun. 2007 Feb 9;353(2):522-6.
[26] Yang YX, Yang AH, Yang ZJ, et al. Involvement of tumor suppressor in lung cancer 1 gene expression in cervieal carcinogenesis. Int J Gynecol Cancer, 2006;16(5):1868-72.
[27] Overmeer RM, Henken FE, Snijders PJ, et al.Association between dense CADM1 promoter methylation and reduced protein expression in high-grade CIN and cervical SCC. J Pathol. 2008 Aug;215(4):388-97.
[28] Kequan Chen , Guanghai Wang , Liang Peng , et al. CADM1/TSLC1 inactivation by promoter hypermethylation is a frequent event in colorectal carcinogenesis and correlates with late stages of the disease. Int J Cancer. 2011 Jan 15;128(2):266-73.
[29] Robb VA, Gerber MA, Hart-Mahon EK, et al. Membrane localization of the U2 domain of Protein 4.1B is necessary and sufficient for meningioma growth suppression. Oncogene. 2005 Mar 10;24(11):1946-57.
[30] Kang Q, Wang T, Zhang H, et al.A Golgi-associated protein 4.1B variant is required for assimilation of proteins in the membrane. J Cell Sci. 2009 Apr 15;122(Pt 8):1091-9.
[31] Jiang W, Newsham IF. The tumor suppressor DAL-1/4.1B and protein methylation cooperate in inducing apoptosis in MCF-7 breast cancer cells.Mol Cancer. 2006 Jan 18;5:4.
[32] Gerber MA, Bahr SM, Gutmann DH.Protein 4.1B/differentially expressed in adenocarcinoma of the lung-1 functions as a growth suppressor in meningioma cells by activating Rac1-dependent c-Jun-NH(2)-kinase signaling. Cancer Res. 2006 May 15;66(10):5295-303.
[33] Dafou D, Grun B, Sinclair J, et al.Microcell-mediated chromosome transfer identifies EPB41L3 as a functional suppressor of epithelial ovarian cancers. Neoplasia. 2010 Jul;12(7):579-89.
[34] Cavanna T, PokornáE, Vesely P, et al. Evidence for protein 4.1B acting as a metastasissuppressor. J Cell Sci. 2007 Feb 15;120(Pt 4):606-16.
[35] Ohno N, Terada N, Murata S, et al. Immunolocalization of protein 4.1B/DAL-1 duringneoplastic transformation of mouse and humanintestinal epithelium. Histochem Cell Biol, 2004;122(6):579-86.
[36] Ohno N, Terada N, Komada M, et al.Dispensable role of protein 4.1B/DAL-1 in rodent adrenal medulla regarding generation of pheochromocytoma and plasmalemmal localization of TSLC1. Biochim Biophys Acta. 2009 Mar;1793(3):506-15.
[1] Kuramochi M, Fukuhara H, Nobukuni T, et al. TSLC1 is a tumorsuppressor gene in human non-small-cell lung cancer. Nature Genetics, 2001;27(4):427-30.
[2] Shingai T, Ikeda W, Kakunaga S, et al.Implications of nectin-like molecule-2/IGSF4/RA175/SgIGSF/TSLC1/SynCAM1 in cell-cell adhesion and transmembrane protein localization in epithelial cells. J Biol Chem, 2003;278(37):35421-7.
[3] Satoh H, Lamb PW, Dong JT et al. Suppression of tumorigenicity of A549 lung adenocarcinoma cells by human chromosomes 3 and 11 introduced via microcell-mediated chromosome transfer. Mol Carcinog 1993; 7: 157–64.
[4] Iizuka M, Sugiyama Y, Shiraishi M, et al. Allelic losses in human chromosome 11 in lung cancers. Genes Chromosomes Cancer 1995; 13: 40–6.
[5] Murakami Y,Nobukuni T,Tamura K,et a1.Localization of tumor suppressor activity impotant in non-small cell lung carcinoma on chromosome 11q[J].Proc Natl Acad Sei USA,1998,95:8153—8158.
[6] Masuda M,Yageta M,Fuukara H,et a1.The tumor suppressor protein TSLCl is involved in cell-cell adhesion [J].J Biol Chem,2002,277(34):31014.
[7] Fujita E,Soyama A,Momoi T.RAl75,which is the mouse ortholog of TSLCI,a tumor suppressor gene in human lung cancer,is a cell adhesion molecule[J].Exp Cell Res,2003,287(1):57.
[8] Wakayama T,Koami H,Ariga H,et a1.Expression and functional characterization of the adhesion molecule spermatogenic immuno-globulin superfamily in the mouse testis[J].Biol Repord,2003,68(5):1755.
[9] Ito A,Jippo T,Wakayama T,et a1.SgIGSF:a newmastcell adhesion molecule used for attachment to fibroblasts and transcriptionally regulated by MITF [J].Blood,2003,101(7):2601.
[10] Biederer T. Bioinformatic characterrization of the SynCAM family of immunoglobulin-like domain-containing adhesion molecules[J].Genomics,2006,87(1):139.
[11] Boles KS,Barchet W,Diacovo T,et a1.The tumor suppressor TSLCl/NECL-2 triggers NK cell and CD8+T cell responses through the cell surface receptor CRTAM[J].Blood,2005,106(3):779.
[12] Galibert L,Diemer GS,Liu Z,et a1.Nectin-like protein 2 defines a subset of T-cell zone dendritic cells and is a ligand for class-I restricted T-cell associated molecule[J].J Biol Chem,2005,280(23):21955.
[13] Das PM,Signal R.DNA methylation and cancer.J Clin Oneol,2004,22:4632—4642.
[14] Gaudet F,Hodgson JG,Eden A,et a1.Induction of tumors in mice by genomie hypomethylation.Science 2003,300:489-492.
[15] Jones PA,Baylin SB.The fundamental role of epigenetic events in cancer.Nat Rev Genet,2002.3:415-428.
[16] Fukuhara H,Kuramoehi M,Fukami T,et a1.Promoter methylation of TSLCl and tumor suppression by its gene product in human prostate cancer[J].Jpn J Cancer Res,2002,93(6):605.
[17] Steenbergen RDM ,Kramer D,Braakhuis BJM. TSLC1 gene silencing in cervical cancer cell lines and cervical neoplasia.J Nail Cancer Inst,200.4,96:294-305.
[18] Honda T, Tamura G, Waki T, et al. Hypermethylation of the TSLC1 gene promoter in primary gastric cancers and gastric cancer cell lines. Jpn J Cancer Res. 2002 Aug;93(8):857-60.
[19] Lung HL, Cheng Y, Kumaran MK, et al. Fine mapping of the 11q22-23 tumor suppressive region and involvement of TSLC1 in nasopharyngeal carcinoma. Int J Cancer. 2004 Nov 20;112(4):628-35.
[20] Hui AB, Lo KW, Kwong J, et al. Epigenetic inactivation of TSLC1 gene in nasopharyngeal carcinoma. Mol Carcinog 2003; 38: 170–8.
[21] Houshmandi SS, Surace EI, Zhang HB, et al. Tumor suppressor in lung cancer-1 (TSLC1) functions as a glioma tumor suppressor. Neurology. 2006 Nov 28;67(10):1863-6.
[22] Dewan MZ, Takamatsu N, Hidaka T, et al. Critical role for TSLC1 expression in the growth and organ infiltration of adult T-cell leukemia cells in vivo.J Virol. 2008 Dec;82(23):11958-63. Epub 2008 Oct 15.
[23] Robb VA, Gerber MA, Hart-Mahon EK, et al. Membrane localization of the U2domain of Protein 4.1B is necessary and sufficient for meningioma growth suppression. Oncogene. 2005 Mar 10;24(11):1946-57.
[24] Kang Q, Wang T, Zhang H, et al.A Golgi-associated protein 4.1B variant is required for assimilation of proteins in the membrane. J Cell Sci. 2009 Apr 15;122(Pt 8):1091-9.
[25] Jiang W, Newsham IF. The tumor suppressor DAL-1/4.1B and protein methylation cooperate in inducing apoptosis in MCF-7 breast cancer cells.Mol Cancer. 2006 Jan 18;5:4.
[26] Gerber MA, Bahr SM, Gutmann DH.Protein 4.1B/differentially expressed in adenocarcinoma of the lung-1 functions as a growth suppressor in meningioma cells by activating Rac1-dependent c-Jun-NH(2)-kinase signaling. Cancer Res. 2006 May 15;66(10):5295-303.
[27] Dafou D, Grun B, Sinclair J, et al.Microcell-mediated chromosome transfer identifies EPB41L3 as a functional suppressor of epithelial ovarian cancers. Neoplasia. 2010 Jul;12(7):579-89.
[28] Cavanna T, PokornáE, Vesely P, et al. Evidence for protein 4.1B acting as a metastasis suppressor. J Cell Sci. 2007 Feb 15;120(Pt 4):606-16.
[29] Ohno N, Terada N, Murata S, et al. Immunolocalization of protein 4.1B/DAL-1 duringneoplastic transformation of mouse and humanintestinal epithelium. Histochem Cell Biol, 2004;122(6):579-86.
[30] Ohno N, Terada N, Komada M, et al.Dispensable role of protein 4.1B/DAL-1 in rodent adrenal medulla regarding generation of pheochromocytoma and plasmalemmal localization of TSLC1. Biochim Biophys Acta. 2009 Mar;1793(3):506-15. Epub 2009 Jan 20.
[31]Harris BZ, Lim WA.Mechanism and role of PDZ domains in signaling complex assembly.J Cell Sci. 2001 Sep;114(Pt 18):3219-31.
[32]Woods DF, Bryant PJ.The discs-large tumor suppressor gene of Drosophila encodes a guanylate kinase homolog localized at septate junctions. Cell. 1991 Aug 9;66(3):451-64.
[33]Ohshiro T, Yagami T, Zhang C, et al. Role of cortical tumour-suppressor proteins in asymmetric division of Drosophila neuroblast.Nature. 2000 Nov 30;408(6812):593-6.
[34]Bella?che Y, Radovic A, Woods DF, et al. The Partner of Inscuteable/Discs-large complex is required to establish planar polarity during asymmetric cell division inDrosophila. Cell. 2001 Aug 10;106(3):355-66.
[35] Ito T, Shimada Y, Hashimoto Y, et al.Involvement of TSLC1 in progression of esophageal squamous cell carcinoma. Cancer Res. 2003 Oct 1;63(19):6320-6.
[36] Tsujiuchi T, Sugata E, Masaoka T, et al. Expression and DNA methylation patterns of Tslc1 and Dal-1 genes in hepatocellular carcinomas induced by N-nitrosodiethylamine in rats. Cancer Sci. 2007 Jul;98(7):943-8. Epub 2007 Apr 12.
[37]李文涛,白华龙,周闯,等.原发性肝癌中抑癌基因TSLC1蛋白的表达及其临床意义.第四军医大学学报. 2007 28(23)
[38] 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. Cancer Biol Ther 2002; 1: 293–6.
[39]刘志清,赵秋,李德民,等.TSLC1和DAL- 1/4.1 B在胰腺癌中的表达及其临床意义.世界华人消化杂志.2008;16(31):3585-3589
[40] Kequan Chen ,Guanghai Wang , Liang Peng , et al.CADM1/TSLC1 inactivation by promoter hypermethylation is a frequent event in colorectal carcinogenesis and correlates with late stages of the disease. Int J Cancer, 2010;
[2] Tran YK, B?gler O, Gorse KM, et al.A novel member of the NF2/ERM/4.1 superfamily with growth suppressing properties in lung cancer. Cancer Res. 1999 Jan 1;59(1):35-43.
[3] Heller G, Geradts J, Ziegler B, et al.Downregulation of TSLC1 and DAL-1 expression occurs frequently in breast cancer. Breast Cancer Res Treat. 2007 Jul;103(3):283-91.
[4] Sakurai-Yageta M, Masuda M, Tsuboi Y, et al.Tumor suppressor CADM1 is involved in epithelial cell structure. Biochem Biophys Res Commun. 2009 Dec 18;390(3):977-82.
[5] Heller G, Fong KM, Girard L, et al.Expression and methylation pattern of TSLC1 cascade genes in lung carcinomas. Oncogene. 2006 Feb 9;25(6):959-68.
[6] Goto A, Niki T, Chi-Pin L, et al. Loss of TSLC1 expression in lung adenocarcinoma: relationships with histological subtypes, sex and prognostic significance. Cancer Sci. 2005 Aug;96(8):480-6.
[7] 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 hypermethylation.Genes Chromosomes Cancer. 2002 Aug;34(4):384-9.
[8] Bertolo C, Guerrero D, Vicente F, et al.Differences and molecular immunohistochemical parameters in the subtypes of infiltrating ductal breast cancer. Am J Clin Pathol. 2008 Sep;130(3):414-24.
[9] Houshmandi SS, Surace EI, Zhang HB, et al. Tumor suppressor in lung cancer-1 (TSLC1) functions as a glioma tumor suppressor. Neurology. 2006 Nov 28;67(10):1863-6.
[10] Fukami T, Fukuhara H, Kuramochi M, et al.Promoter methylation of the TSLC1 gene in advanced lung tumors and various cancer cell lines. Int J Cancer. 2003 Oct 20;107(1):53-9.
[11] Uchino K, Ito A, Wakayama T, et al.Clinical implication and prognostic significance of the tumor suppressor TSLC1 gene detected in adenocarcinoma of the lung. Cancer. 2003 Sep 1;98(5):1002-7.
[12] Kikuchi S, Yamada D, Fukami T, et al.Hypermethylation of the TSLC1/IGSF4promoter is associated with tobacco smoking and a poor prognosis in primary nonsmall cell lung carcinoma. Cancer. 2006 Apr 15;106(8):1751-8.
[13] Kitamura Y, Kurosawa G, Tanaka M, et al.Frequent overexpression of CADM1/IGSF4 in lung adenocarcinoma. Biochem Biophys Res Commun. 2009 Jun 12;383(4):480-4.
[14] Michels E, Hoebeeck J, De Preter K, et al.CADM1 is a strong neuroblastoma candidate gene that maps within a 3.72 Mb critical region of loss on 11q23. BMC Cancer. 2008 Jun 17;8:173.
[15] Nowacki S, Skowron M, Oberthuer A, et al.Expression of the tumour suppressor gene CADM1 is associated with favourable outcome and inhibits cell survival in neuroblastoma. Oncogene. 2008 May 22;27(23):3329-38.
[16] Fukuhara H, Kuramochi M, Fukami T, et al. Promoter methylation of TSLC1 and tumor suppression by its gene product in human prostate cancer. Jpn J Cancer Res. 2002 Jun;93(6):605-9.
[17] Williams YN, Masuda M, Sakurai-Yageta M, et al.Cell adhesion and prostate tumor-suppressor activity of TSLL2/IGSF4C, an immunoglobulin superfamily molecule homologous to TSLC1/IGSF4. Oncogene. 2006 Mar 9;25(10):1446-53.
[18] Murakami Y.Functional cloning of a tumor suppressor gene, TSLC1, in human non-small cell lung cancer. Oncogene. 2002 Oct 7;21(45):6936-48.
[19]Qin L, Zhu W, Xu T, et al.Effect of TSLC1 gene on proliferation, invasion and apoptosis of human hepatocellular carcinoma cell line HepG2. J Huazhong Univ Sci Technolog Med Sci. 2007 Oct;27(5):535-7.
[20] Honda T, Tamura G, Waki T, et al. Hypermethylation of the TSLC1 gene promoter in primary gastric cancers and gastric cancer cell lines. Jpn J Cancer Res. 2002 Aug;93(8):857-60.
[21] Lung HL, Cheng Y, Kumaran MK, et al. Fine mapping of the 11q22-23 tumor suppressive region and involvement of TSLC1 in nasopharyngeal carcinoma. Int J Cancer. 2004 Nov 20;112(4):628-35.
[22] Hui AB, Lo KW, Kwong J, et al. Epigenetic inactivation of TSLC1 gene in nasopharyngeal carcinoma. Mol Carcinog 2003; 38: 170–8.
[23] Ito T, Shimada Y, Hashimoto Y, et al. Involvement of TSLCI in progression ofesophageal squamous cell carcinoma. Cancer Res,2003,63(19):6320-6.
[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. Cancer Biol Ther 2002; 1: 293-6.
[25] Shimizu K, Onishi M, Sugata E, et al. Aberrant DNA methylation of the 5' upstream region of Tslc1 gene in hamster pancreatic tumors. Biochem Biophys Res Commun. 2007 Feb 9;353(2):522-6.
[26] Yang YX, Yang AH, Yang ZJ, et al. Involvement of tumor suppressor in lung cancer 1 gene expression in cervieal carcinogenesis. Int J Gynecol Cancer, 2006;16(5):1868-72.
[27] Overmeer RM, Henken FE, Snijders PJ, et al.Association between dense CADM1 promoter methylation and reduced protein expression in high-grade CIN and cervical SCC. J Pathol. 2008 Aug;215(4):388-97.
[28] Kequan Chen , Guanghai Wang , Liang Peng , et al. CADM1/TSLC1 inactivation by promoter hypermethylation is a frequent event in colorectal carcinogenesis and correlates with late stages of the disease. Int J Cancer. 2011 Jan 15;128(2):266-73.
[29] Robb VA, Gerber MA, Hart-Mahon EK, et al. Membrane localization of the U2 domain of Protein 4.1B is necessary and sufficient for meningioma growth suppression. Oncogene. 2005 Mar 10;24(11):1946-57.
[30] Kang Q, Wang T, Zhang H, et al.A Golgi-associated protein 4.1B variant is required for assimilation of proteins in the membrane. J Cell Sci. 2009 Apr 15;122(Pt 8):1091-9.
[31] Jiang W, Newsham IF. The tumor suppressor DAL-1/4.1B and protein methylation cooperate in inducing apoptosis in MCF-7 breast cancer cells.Mol Cancer. 2006 Jan 18;5:4.
[32] Gerber MA, Bahr SM, Gutmann DH.Protein 4.1B/differentially expressed in adenocarcinoma of the lung-1 functions as a growth suppressor in meningioma cells by activating Rac1-dependent c-Jun-NH(2)-kinase signaling. Cancer Res. 2006 May 15;66(10):5295-303.
[33] Dafou D, Grun B, Sinclair J, et al.Microcell-mediated chromosome transfer identifies EPB41L3 as a functional suppressor of epithelial ovarian cancers. Neoplasia. 2010 Jul;12(7):579-89.
[34] Cavanna T, PokornáE, Vesely P, et al. Evidence for protein 4.1B acting as a metastasissuppressor. J Cell Sci. 2007 Feb 15;120(Pt 4):606-16.
[35] Ohno N, Terada N, Murata S, et al. Immunolocalization of protein 4.1B/DAL-1 duringneoplastic transformation of mouse and humanintestinal epithelium. Histochem Cell Biol, 2004;122(6):579-86.
[36] Ohno N, Terada N, Komada M, et al.Dispensable role of protein 4.1B/DAL-1 in rodent adrenal medulla regarding generation of pheochromocytoma and plasmalemmal localization of TSLC1. Biochim Biophys Acta. 2009 Mar;1793(3):506-15.
[1] Kuramochi M, Fukuhara H, Nobukuni T, et al. TSLC1 is a tumorsuppressor gene in human non-small-cell lung cancer. Nature Genetics, 2001;27(4):427-30.
[2] Shingai T, Ikeda W, Kakunaga S, et al.Implications of nectin-like molecule-2/IGSF4/RA175/SgIGSF/TSLC1/SynCAM1 in cell-cell adhesion and transmembrane protein localization in epithelial cells. J Biol Chem, 2003;278(37):35421-7.
[3] Satoh H, Lamb PW, Dong JT et al. Suppression of tumorigenicity of A549 lung adenocarcinoma cells by human chromosomes 3 and 11 introduced via microcell-mediated chromosome transfer. Mol Carcinog 1993; 7: 157–64.
[4] Iizuka M, Sugiyama Y, Shiraishi M, et al. Allelic losses in human chromosome 11 in lung cancers. Genes Chromosomes Cancer 1995; 13: 40–6.
[5] Murakami Y,Nobukuni T,Tamura K,et a1.Localization of tumor suppressor activity impotant in non-small cell lung carcinoma on chromosome 11q[J].Proc Natl Acad Sei USA,1998,95:8153—8158.
[6] Masuda M,Yageta M,Fuukara H,et a1.The tumor suppressor protein TSLCl is involved in cell-cell adhesion [J].J Biol Chem,2002,277(34):31014.
[7] Fujita E,Soyama A,Momoi T.RAl75,which is the mouse ortholog of TSLCI,a tumor suppressor gene in human lung cancer,is a cell adhesion molecule[J].Exp Cell Res,2003,287(1):57.
[8] Wakayama T,Koami H,Ariga H,et a1.Expression and functional characterization of the adhesion molecule spermatogenic immuno-globulin superfamily in the mouse testis[J].Biol Repord,2003,68(5):1755.
[9] Ito A,Jippo T,Wakayama T,et a1.SgIGSF:a newmastcell adhesion molecule used for attachment to fibroblasts and transcriptionally regulated by MITF [J].Blood,2003,101(7):2601.
[10] Biederer T. Bioinformatic characterrization of the SynCAM family of immunoglobulin-like domain-containing adhesion molecules[J].Genomics,2006,87(1):139.
[11] Boles KS,Barchet W,Diacovo T,et a1.The tumor suppressor TSLCl/NECL-2 triggers NK cell and CD8+T cell responses through the cell surface receptor CRTAM[J].Blood,2005,106(3):779.
[12] Galibert L,Diemer GS,Liu Z,et a1.Nectin-like protein 2 defines a subset of T-cell zone dendritic cells and is a ligand for class-I restricted T-cell associated molecule[J].J Biol Chem,2005,280(23):21955.
[13] Das PM,Signal R.DNA methylation and cancer.J Clin Oneol,2004,22:4632—4642.
[14] Gaudet F,Hodgson JG,Eden A,et a1.Induction of tumors in mice by genomie hypomethylation.Science 2003,300:489-492.
[15] Jones PA,Baylin SB.The fundamental role of epigenetic events in cancer.Nat Rev Genet,2002.3:415-428.
[16] Fukuhara H,Kuramoehi M,Fukami T,et a1.Promoter methylation of TSLCl and tumor suppression by its gene product in human prostate cancer[J].Jpn J Cancer Res,2002,93(6):605.
[17] Steenbergen RDM ,Kramer D,Braakhuis BJM. TSLC1 gene silencing in cervical cancer cell lines and cervical neoplasia.J Nail Cancer Inst,200.4,96:294-305.
[18] Honda T, Tamura G, Waki T, et al. Hypermethylation of the TSLC1 gene promoter in primary gastric cancers and gastric cancer cell lines. Jpn J Cancer Res. 2002 Aug;93(8):857-60.
[19] Lung HL, Cheng Y, Kumaran MK, et al. Fine mapping of the 11q22-23 tumor suppressive region and involvement of TSLC1 in nasopharyngeal carcinoma. Int J Cancer. 2004 Nov 20;112(4):628-35.
[20] Hui AB, Lo KW, Kwong J, et al. Epigenetic inactivation of TSLC1 gene in nasopharyngeal carcinoma. Mol Carcinog 2003; 38: 170–8.
[21] Houshmandi SS, Surace EI, Zhang HB, et al. Tumor suppressor in lung cancer-1 (TSLC1) functions as a glioma tumor suppressor. Neurology. 2006 Nov 28;67(10):1863-6.
[22] Dewan MZ, Takamatsu N, Hidaka T, et al. Critical role for TSLC1 expression in the growth and organ infiltration of adult T-cell leukemia cells in vivo.J Virol. 2008 Dec;82(23):11958-63. Epub 2008 Oct 15.
[23] Robb VA, Gerber MA, Hart-Mahon EK, et al. Membrane localization of the U2domain of Protein 4.1B is necessary and sufficient for meningioma growth suppression. Oncogene. 2005 Mar 10;24(11):1946-57.
[24] Kang Q, Wang T, Zhang H, et al.A Golgi-associated protein 4.1B variant is required for assimilation of proteins in the membrane. J Cell Sci. 2009 Apr 15;122(Pt 8):1091-9.
[25] Jiang W, Newsham IF. The tumor suppressor DAL-1/4.1B and protein methylation cooperate in inducing apoptosis in MCF-7 breast cancer cells.Mol Cancer. 2006 Jan 18;5:4.
[26] Gerber MA, Bahr SM, Gutmann DH.Protein 4.1B/differentially expressed in adenocarcinoma of the lung-1 functions as a growth suppressor in meningioma cells by activating Rac1-dependent c-Jun-NH(2)-kinase signaling. Cancer Res. 2006 May 15;66(10):5295-303.
[27] Dafou D, Grun B, Sinclair J, et al.Microcell-mediated chromosome transfer identifies EPB41L3 as a functional suppressor of epithelial ovarian cancers. Neoplasia. 2010 Jul;12(7):579-89.
[28] Cavanna T, PokornáE, Vesely P, et al. Evidence for protein 4.1B acting as a metastasis suppressor. J Cell Sci. 2007 Feb 15;120(Pt 4):606-16.
[29] Ohno N, Terada N, Murata S, et al. Immunolocalization of protein 4.1B/DAL-1 duringneoplastic transformation of mouse and humanintestinal epithelium. Histochem Cell Biol, 2004;122(6):579-86.
[30] Ohno N, Terada N, Komada M, et al.Dispensable role of protein 4.1B/DAL-1 in rodent adrenal medulla regarding generation of pheochromocytoma and plasmalemmal localization of TSLC1. Biochim Biophys Acta. 2009 Mar;1793(3):506-15. Epub 2009 Jan 20.
[31]Harris BZ, Lim WA.Mechanism and role of PDZ domains in signaling complex assembly.J Cell Sci. 2001 Sep;114(Pt 18):3219-31.
[32]Woods DF, Bryant PJ.The discs-large tumor suppressor gene of Drosophila encodes a guanylate kinase homolog localized at septate junctions. Cell. 1991 Aug 9;66(3):451-64.
[33]Ohshiro T, Yagami T, Zhang C, et al. Role of cortical tumour-suppressor proteins in asymmetric division of Drosophila neuroblast.Nature. 2000 Nov 30;408(6812):593-6.
[34]Bella?che Y, Radovic A, Woods DF, et al. The Partner of Inscuteable/Discs-large complex is required to establish planar polarity during asymmetric cell division inDrosophila. Cell. 2001 Aug 10;106(3):355-66.
[35] Ito T, Shimada Y, Hashimoto Y, et al.Involvement of TSLC1 in progression of esophageal squamous cell carcinoma. Cancer Res. 2003 Oct 1;63(19):6320-6.
[36] Tsujiuchi T, Sugata E, Masaoka T, et al. Expression and DNA methylation patterns of Tslc1 and Dal-1 genes in hepatocellular carcinomas induced by N-nitrosodiethylamine in rats. Cancer Sci. 2007 Jul;98(7):943-8. Epub 2007 Apr 12.
[37]李文涛,白华龙,周闯,等.原发性肝癌中抑癌基因TSLC1蛋白的表达及其临床意义.第四军医大学学报. 2007 28(23)
[38] 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. Cancer Biol Ther 2002; 1: 293–6.
[39]刘志清,赵秋,李德民,等.TSLC1和DAL- 1/4.1 B在胰腺癌中的表达及其临床意义.世界华人消化杂志.2008;16(31):3585-3589
[40] Kequan Chen ,Guanghai Wang , Liang Peng , et al.CADM1/TSLC1 inactivation by promoter hypermethylation is a frequent event in colorectal carcinogenesis and correlates with late stages of the disease. Int J Cancer, 2010;