EBV LMP1通过诱导c-myc表达活化端粒酶hTERT  

Epstein-Barr Virus LMP1 Activates Human Telomerase Transcription via c-myc Expression

作　　者：杨静[1] 邓锡云[1] 邓琳[1] 丁琳[1] 顾焕华[1] 易薇[1] 曹亚[1] 

机构地区：[1]中南大学湘雅医学院肿瘤研究所,长沙410078

出　　处：《病毒学报》2003年第3期240-244,共5页Chinese Journal of Virology

基　　金：国家重点基础研究发展规划(973);"鼻咽癌发生发展的基础研究"(G1998051201);国家自然科学基金面上项目(30200328);美国中华医学基金(CMB96655)。

摘　　要：利用原代人胚鼻咽上皮细胞和Tet on LMP1HNE2等良好的细胞体系,采用报道基因法和Westernblot法等,分别检测Epstein Barr病毒(EBV)潜伏膜蛋白1(LMP1)诱导的c myc反式激活活性和蛋白表达水平,从LMP1诱导细胞内c myc表达的角度,探讨LMP1诱导端粒酶表达的分子机制。结果表明,LMP1促使细胞内c myc反式激活活性增强,c Myc蛋白表达量升高;导入反义LMP1表达质粒阻断LMP1表达后,c myc反式激活活性下降。将端粒酶hTERT启动子上c myc结合位点突变后,LMP1不能诱导端粒酶hTERT表达。因而认为,EB病毒LMP1通过诱导c myc表达而活化端粒酶hTERT。Latent membrane protein 1 (LMP1), one of the oncoprotein enco ded by Epstein-Barr virus,is suffi cient for development of nasophary ngeal carcinoma in vivo and naso pharyngeal epithelial cell immortali zation in vitro.Aslo, it has bee n shown to increase the telomerase en zyme activity in primary human nas opharyngeal epithelial cells by an unknown mechanism.We report here that a study using reporter gene as say in transduced primary human na sopharyngeal epithelial cells and a Tet-on-LPM1 nasopharyngeal carci noma cell line,named Tet-on-LMP1 H NE2 shows that LMP1 induces c-myc protein expression and enhances th e transactivation of c-myc.Mutati on of the minimal hTERT promoter c ontaining c-myc-responsive E-box e lements can down-regulate the expr ession of hTERT induced by LMP1,su ggesting a role for c-myc protein in LMP1 mediated telomerase reacti vation.These findings suggest that telomerase is a target of LMP1 and telomerase activation by LMP1 is t hrough c-myc expression.

关 键 词：端粒酶 潜伏膜蛋白1 鼻咽癌 EB病毒 

分 类 号：R730[医药卫生—肿瘤] R373.9[医药卫生—临床医学]