EB病毒感染人胎鼻咽上皮细胞逃避老化期过程中抑制p16^(INK4a)表达

EPSTEIN-BARR VIRUS INHIBITS P16^(INK4a) EXPRESSION IN HUMAN FETAL NASOPHARYNGEAL EPITHELIAL CELLS ESCAPING FROM THE REPLICATIVE SENENSCENCE

细胞周期调控紊乱是细胞永生化进程中一个重要的分子事件,本文利用Western blotting和S-P法分别检测p16^(INK4a)、p53、p21^(WAF1/CIP1)和E2F1的蛋白表达,试图从细胞周期调控的角度,探讨EB病毒诱导人胎鼻咽上皮细胞逃避老化期的分子机制。结果表明,EB病毒通过抑制p16^(INK4a)表达而阻断p16^(INK4a)/Rb途径,上调转录因子E2F1,而对p53、p21^(WAF1/CIP1)表达无明显的影响。结果初步揭示,EB病毒介导的p16^(INK4a)/Rb/E2F1细胞周期调控紊乱参与了人胎鼻咽上皮细胞逃避老化期过程,为进一步探讨鼻咽癌发病机制提供了科学依据。

Cell cycle deregulation is regarded as an important event to involve in cellular immortalization. To confirm the role of cell cycle deregulation in human fetal nasopharyngeal epithelial cells escaping from the replicative senescence induced by Epstein-Barr virus infection, we detected expression of cell cycle regulators, such as p16INK4a, p21WAF1/CIP1, p53, and E2F1 with Western blotting and im-munocytochemisty in this study. Our results found that Epstein-Barr virus inhibited the expression of p16INK4a, at the same time, E2F1 expression were strongly increased in EBV-infected cells, however, as for the expression of p53 and p21WAF1/CIP1, there was no difference between EBV-infected cells and non-infected cells. The results show that EBV inactivates p16INK4a/pRB pathway and then induces E2F1 activity and it is implicated that Epstein-Barr virus-medicated cell cycle deregulation plays an important role in the immortalization of human nasopharyngeal epithelial cells. These data will be helpful for further studying the carcinogenesis of nasopharyngeal carcinoma.