The Epstein-Barr virus oncogene product, latent membrane protein 1, induces the downregulation of E-cadherin gene expression via activation of DNA methyltransferases  

作　　者：Chi-NeuTsai 

机构地区：[1]GraduateInstituteofBasicMedicalSciences,Chang-GungUniversity.Kwei-shan,Taoyuan.Taiwan333,RepublicofChina [2]GraduateInstituteofMicrobiologyandImmunology,Yang-MingUniversity,Shih-Pai,Taipei,Taiwan112,RepublicofChina

出　　处：《中国生物学文摘》2005年第4期86-91,共6页Chinese Biological Abstracts

摘　　要：The latent membrane protein (LMP1) of Epstein-Barr virus (EBV) is expressed in EBV-associated nasopharyngeal carcinoma, which isnotoriously metastatic. Although it Is established that LMP1 represses E-cadherin expression and enhances the invasive ability of carcinoma cells, the mechanism underlying this repression remains to be elucidated. In this study, we demonstrate that LMP1 induces the expression and activity of the DNA methyltransferases 1, 3a, and 3b, using real-time reverse transcription-PCR and enzyme activity assay. This results in hypermethylation of the E-cadherin promoter and down-regulation of E-cadherin gene expression, as revealed by methylation-specific PCR, real-time reverse transcription-PeR and Western blotting data. The DNA methyltransferase inhibitor, 5'-Aza-2'dC, restores E-cadherin promoter activity and protein expression in LMPl-expressing cells, which in turn blocks cell migration ability, as demonstrated by the Transwell cell migration assay. Our findings suggest that LMP1 down-regulates E-cadherin gene expression and induces cell migration activity by using cellular DNA methylation machinery.

关 键 词：爱波斯坦-巴尔病毒 致癌基因 DNA甲基转移酶 DNA甲基化 基因表达 膜蛋白质 PCR 鼻咽癌 

分 类 号：R739.63[医药卫生—肿瘤] R730.2[医药卫生—临床医学]