Ding Lin, Li Lili, Yang Jing, Zhou Shanghui, Li Wei, Tang Min, Shi Ying, Yi Wei, Cao Ya
Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
J Med Virol. 2007 Aug;79(8):1153-63. doi: 10.1002/jmv.20896.
Elevated telomerase activity is observed in about 90% of human cancers. This activity correlates strictly with human telomerase reverse transcriptase (hTERT). Previously, it was shown that the Epstein-Barr virus-encoded latent membrane protein 1 (LMP1) induced telomerase activity in nasopharyngeal carcinoma cells. In this study, it was indicated that LMP1 inhibited p16(INK4A) expression, promoted phosphorylation of p105 Rb and upregulated E2F1 expression as well as transactivation, and overexpression of E2F1 alone was sufficient to upregulate telomerase activity. The JNK kinase cascade could also promote telomerase activity modulated by LMP1, that inhibition of JNK by JIP and TAM 67 dominant negative mutant abrogated telomerase activity. The data show that p16(INK4A)/Rb/E2F1 and JNK signaling pathways are involved in the regulation of telomerase activity via LMP1. The present study provides new perspectives on carcinogenesis of nasopharyngeal carcinoma that may be exploited for novel therapeutic strategies.
在大约90%的人类癌症中观察到端粒酶活性升高。这种活性与人类端粒酶逆转录酶（hTERT）密切相关。此前有研究表明，爱泼斯坦-巴尔病毒编码的潜伏膜蛋白1（LMP1）可诱导鼻咽癌细胞中的端粒酶活性。在本研究中，结果表明LMP1抑制p16（INK4A）表达，促进p105 Rb磷酸化，上调E2F1表达及其反式激活，单独过表达E2F1就足以上调端粒酶活性。JNK激酶级联反应也可促进LMP1调节的端粒酶活性，JIP和TAM 67显性负性突变体对JNK的抑制可消除端粒酶活性。数据表明，p16（INK4A）/Rb/E2F1和JNK信号通路参与了LMP1对端粒酶活性的调节。本研究为鼻咽癌的致癌机制提供了新的视角，有望用于开发新的治疗策略。
