食管癌细胞中T钙黏蛋白基因启动子区异常甲基化的研究  

Aberrant methylation of T-cadherin gene in human esophageal carcinoma cells

作　　者：景钊[1] 邹长林[1] 李刚[1] 邓霞[1] 吴式琇[1] 

机构地区：[1]温州医学院附属第一医院放化疗科,325000

出　　处：《中华医学杂志》2011年第37期2653-2656,共4页National Medical Journal of China

摘　　要：目的探讨食管癌细胞中T钙黏蛋白（T—cadherin）基因启动子区甲基化状态，以及5-杂氮-2’-脱氧胞苷（5-Aza—CdR）作用对食管癌细胞生长、侵袭以及T—cadherin基因甲基化状态与表达的影响。方法采用甲基化特异性PCR分析经5-Aza-CdR处理前后食管癌细胞EC1和EC109中T—cadherin启动子甲基化状态，Western印迹检测经5-Aza—CdR处理前后两种细胞中T—cadherin蛋白表达，以M1T11比色法与侵袭实验测定细胞增殖与侵袭能力的变化。结果EC1和EC109细胞中T—cadherin基因启动子区域存在异常甲基化现象，经5-Aza—CdR作用后可逆转启动子异常甲基化，显著上调食管癌细胞中T—cadherin的蛋白表达，同时显著抑制肿瘤细胞的增殖与侵袭能力（P〈0．01）。结论启动子区异常甲基化是导致食管癌细胞中T—cadherin表达水平下调的重要机制，应用5-Aza—CdR可恢复T—cadherin表达并抑制肿瘤细胞的恶性表型。Objective To explore the methylation status of T-cadherin promoter region in human esophageal carcinoma cell lines EC1 and EC109 and elucidate the effects of 5-azacytidine-2＇-deoxycytidines （5-Aza-CdR） on their abilities of proliferation and invasion, the methylation status and the expression of T- cadherin. Methods The expression level of T-cadherin was measured by Western blot. And the methylation status of T-cadherin promoter region was analyzed by methylation-specific PCR （polymerase ehian reaction）, separately before and after a treatment of demethylating agent 5-Aza-CdR. Results The T-cadhefin gene was hypermethylated in EC109 cells but semi-methylated in EC1 ceils. After a treatment of 5-Aza-CdR, T- cadherin gene methylation was reversed. And the gene expression was strongly up-regulated in both cells. 5- Aza-CdR could decrease the proliferation and effectively inhibit the ability of cell invasion （ P 〈 0. 01 ）. Conclusion The aberrant methylation in promoter region is an important mechanism of T-cadherin gene inactivation in human esophageal carcinoma cells. 5-Aza-CdR can increase the expression of T-cadherin by a reversal of hypermethylation and effectively inhibit the proliferation and invasion of tumor cells.

关 键 词：食管肿瘤 甲基化 钙黏着糖蛋白类 

分 类 号：R735.1[医药卫生—肿瘤]