肝癌细胞端粒酶激活的可能机制:乙型肝炎病毒x基因-端粒酶反转录酶途径

A potential mechanism of telomerase activation in hepatocellular carcinoma cells:hepatitis virus x gene-telomerase reverse transcriptase path way

目的 研究乙型肝炎病毒x基因 (HBx)对肝癌细胞端粒酶活性及其催化亚单位端粒酶反转录酶 (TERT)表达的影响 ,探讨肝癌细胞端粒酶激活的分子机制。方法 分别应用端粒序列重复扩增法 (TRAP)和定量逆转录 聚合酶链反应 (RT PCR)检测QGY770 1肝癌细胞株 (n=5 )和转HBx基因肝癌细胞株QGY/HBx(n =5 )的端粒酶活性及TERTmRNA表达。结果 HBx阳性的QGY/HBx肝癌细胞TERT基因表达水平 1.5 4± 0 .14较HBx阴性的QGY770 1肝癌细胞0 .76± 0 .0 8明显增高 (P <0 .0 1) ;与之对应 ,QGY/HBx细胞的端粒酶活性也显著高于QGY770 1细胞 [( 4.2 8± 2 .81)× 10 5比 ( 2 .43± 1.46)× 10 5,P <0 .0 5 ]。结论 HBx基因可增强肝癌细胞端粒酶活性 ,上调TERT基因表达 ;HBx TERT途径可能是肝癌细胞端粒酶端粒激活的一个重要机制。

Objective To study the effects of hepat it is virus x gene (HBx gene) on the activity of telomerase and the expression of t elomerase reverse transcriptase (TERT) gene and investigate the molecular mechan ism of the activation of telomerase in hepatocellular carcinoma (HCC) cells.Methods By means of TRAP and quantitative RT-PCR techniq ues,the activities of telomerase and the levels of TERT mRNA were detected in Q GY7701 HCC cell line and QGY/HBx HCC cell line with HBx gene modified.Results The expression levels of TERT mRNA in HBx positiv e QGY/HBx cells (1.54±)(0.14) were significantly increased as compared with those in the HBx negative QGY7701 cells (0.76±)(0.08,)(P<0.01).Accord ingly,the a ctivities of telomerase in QGY/HBx cells [(4.28±2.81)×10~5] were higher th an in QGY7701 cells [(2.43±1.46)×10~5,P<0.05].Conclusion The HBx gene could improve the activity of tel omerase and upregulate the expression of TERT gene in HCC cells.HBx-TERT pathwa y might be an important mechanism to activate the telomerase of HCC cells.