EB病毒潜伏膜蛋白1诱导人鼻咽上皮细胞端粒酶的表达

EPSTEIN-BARR VIRUS LATENT MEMBRANE PROTEIN 1 INDUCES THE TELOMERASE ACTIVITY IN HUMAN NASOPHARYNGEAL EPITHELIAL CELLS

上皮细胞逃避老化期是细胞永生化过程中一个重要分子事件,端粒酶活性表达是维持人染色体端粒长度、抑制细胞进入老化期的关键因素之一。我们利用最新的端粒酶PCR-ELISA半定量技术,检测永生化早期阶段人胚鼻咽上皮细胞中端粒酶表达的情况,探讨EB病毒在人胚鼻咽上皮细胞永生化过程中的分子机制。结果表明,EB病毒诱导老化前期人胚鼻咽上皮细胞端粒酶表达,从而促使人胚鼻咽上皮细胞逃避老化期、进入永生化早期阶段。此外,我们还首次发现,人胚鼻咽上皮细胞表达端粒酶活性依赖于EB病毒LMP1蛋白的表达水平和LMP1分子的完整性,LMP1可能通过诱导端粒酶活性表达促进人鼻咽上皮细胞永生化。我们的实验为进一步探讨EB病毒诱导人胚鼻咽上皮细胞永生化的作用机制提供了实验基础。

Telomerase activation has been linked to cell immortalization in vitro and tumorigenicity in vivo. In this study, for the first, we reported that Epstein-Barr virus activated the telomerase activity of human nasopharyngeal epithelial cells in the early stage of immortalization as tested by the PCR-ELISA. The telomerase activity in na-sopharyngeal epithelial cells was only observed in pre-senescent cells. It was implicated that Epstein-Barr virus induced the escape of nasopharyngeal epithelial cells from senescence via the activation of telomerase. We further showed that telomerase activation in infected cells was de- pendent on the protein level of latent membrane protein 1 (LMP1) encoded by Epstein-Barr virus using a Tetracy-cline regulatory cell line expressing LMP1 , pTet-on-LMP1-HNE2. The activity of telomerase in nasopharyngeal cells was decreased when the protein level of LMP1 was blocked by antisense LMP1 plasrnid DNA. And the activity of telomerase was also related to the carboxyl terminus of LMP1. It was implicated that the ability of Epstein - Barr virus to suppress senescence is associated with telomerase activation by LMP1.