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Promoter methylation and expression of tissue inhibitor of metalloproteinase 3 gene in gastric cancer
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- Author:
- No author available
- Journal Title:
- WORLD CHINESE JOURNAL OF DIGESTOLOGY
- Issue:
- 2
- DOI:
- 10.3969/j.issn.1009-3079.2006.02.003
- Key Word:
- 胃癌;TIMP3;CpG岛;甲基化
Abstract： 目的:探讨组织金属蛋白酶抑制因子-3(tissueinhibitor of metalloproteinase 3,TIMP3)基因启动子甲基化与其蛋白表达的相关性,并分析TIMP3基因CpG岛异常甲基化与胃腺癌及其临床病理特征的关联性,方法:应用甲基化特异性PCR(MSP)技术和免疫组织化学方法分别检测78例患者的胃正常黏膜组织、胃癌组织及转移淋巴结中,TIMP3基因启动子甲基化和蛋白表达情况.结果:胃正常黏膜组织、早期、进展期胃癌组织和转移淋巴结中TIMP3基因启动子均有甲基化修饰,其阳性率分别为35.9%(28/78);85.0%(17/20),89.7%(52/58);转移淋巴结100%(78/78).胃癌组TIMP3基因启动子甲基化率明显高于胃正常黏膜组(P＜0.05).胃正常黏膜组织TIMP3蛋白表达全部为阳性(100%),20例早期胃癌中,6例阳性(30%),58例进展期胃癌中,2例阳性(3.4%),在转移淋巴结中全部不表达(0%).胃癌70例蛋白表达阴性的标本中,64例TIMP3基因启动子甲基化阳性(91.4%),TIMP3蛋白表达与启动子甲基化呈明显负相关(P＜0.01).结论:启动子区CpG岛高甲基化是胃癌组织中TIMP3基因表达失活的主要机制,可能成为胃癌分子诊断与病期评估的标志之一.
- [1]Jing-Yuan Fang,You-Yong Lu.Effects of histone acetylation and DNA methylation on p21WAF1 regulation[J].2002,(3).
- [2]V, Colot,L, Maloisel,J L, Rossignol.[DNA repeats and homologous recombination: a probable role for DNA methylation in genome stability of eukaryotic cells].[J].1999,193.
- [3]Kim JC,Ro JY,Lee S,etc.Profile of methylated CpG sites of hMLH1 promoter in primary gastric carcinoma with microsatellite instability.[J].2002,52(12).
- [4]James G. Herman,Jeremy R. Graff,Sanna Myohanen.Methylation-specific PCR: A novel PCR assay for methylation status of CpG islands[J].1996,93(18).
- [5]R S, Kerbel.Growth dominance of the metastatic cancer cell: cellular and molecular aspects.[J].1990,55.
- [6]M R, Smith,H, Kung,S K, Durum,etc.TIMP-3 induces cell death by stabilizing TNF-alpha receptors on the surface of human colon carcinoma cells.[J].1997,9.
- [7]Lee HJ,Kim JS,Kang GH,etc.Aberrant CpG island hypermethylation of multiple genes in colorectal neoplasia.[J].2004,84(7).
- [8]Noh SH,Kim H,Kim NG,etc.Concerted promoter hypermethylation of hMLH1, p16INK4A, and E-cadherin in gastric carcinomas with microsatellite instability.[J].2003,200(1).
- [9]Naoki, Kimura,Takeshi, Nagasaka,Jun, Murakami,etc.Methylation profiles of genes utilizing newly developed CpG island methylation microarray on colorectal cancer patients.[J].2005,33.
- [10]Waterhouse P,Gowing KL,Poole AR,etc.Spontaneous air space enlargement in the lungs of mice lacking tissue inhibitor of metalloproteinases-3 (TIMP-3).[J].2001,108(6).
- [11]Nakayama H,Matsusaki K,Taniyama K,etc.Reduced expression of the TSP1 gene and its association with promoter hypermethylation in gastric carcinoma.[J].2003,64(4).
- [12]F, Mannello,G, Gazzanelli.Tissue inhibitors of metalloproteinases and programmed cell death: conundrums, controversies and potential implications.[J].2001,6(6).
- [13]Leslie H. Sobin M.D.,Irvin D. Fleming M.D..TNM classification of malignant tumors, fifth edition (1997)[J].1997,80(9).
- [14]S B, Baylin,J G, Herman.DNA hypermethylation in tumorigenesis: epigenetics joins genetics.[J].2000,16(4).
- [15]Hurtubise A,Gagnon J,Shaker S,etc.Interaction of 5-aza-2'-deoxycytidine and depsipeptide on antineoplastic activity and activation of 14-3-3sigma, E-cadherin and tissue inhibitor of metalloproteinase 3 expression in human breast carcinoma cells.[J].2003,14(3).
- [16]Cheong KF,Ward RL,Tomlinson I,etc.CpG island methylation is a common finding in colorectal cancer cell lines.[J].2003,88(3).
- [17]Michio Shimizu,Yoichi Saitoh,Hiroshi Itoh.Immunohistochemical staining of Ha-ras oncogene product in normal, benign, and malignant human pancreatic tissues[J].1990,21(6).
- [18]M, Vogelauer,J, Wu,N, Suka,etc.Global histone acetylation and deacetylation in yeast.[J].2000,408(6811).