Chang J, Yang S H, Cho Y G, Hwang S B, Hahn Y S, Sung Y C
Department of Life Science, School of Environmental Engineering, Pohang University of Science and Technology, Kyungbuk, Republic of Korea.
J Virol. 1998 Apr;72(4):3060-5. doi: 10.1128/JVI.72.4.3060-3065.1998.
Persistent infection with hepatitis C virus (HCV) is associated with the development of liver cirrhosis and hepatocellular carcinoma. To examine the oncogenic potential of the HCV core gene product, primary rat embryo fibroblasts (REFs) were transfected with the core gene in the presence or absence of the H-ras oncogene. In contrast to a previous report (R. B. Ray, L. M. Lagging, K. Meyer, and R. Ray, J. Virol. 70:4438-4443, 1996), HCV core proteins from two different genotypes (type 1a and type 1b) were not found to transform REFs to tumorigenic phenotype in cooperation with the H-ras oncogene, although the core protein was successfully expressed 20 days after transfection. In addition, REFs transfected with E1A- but not core-expressing plasmid showed the phenotype of immortalized cells when selected with G418. The biological activity was confirmed by observing the transcription activation from two viral promoters, Rous sarcoma virus long terminal repeat and simian virus 40 promoter, which are known to be activated by the core protein from HCV-1 isolate. In contrast to the result with primary cells, the Rat-1 cell line, stably expressing HCV core protein, exhibited focus formation, anchorage-independent growth, and tumor formation in nude mice. HCV core protein was able to induce the transformation of Rat-1 cells with various efficiencies depending on the expression level of the core protein. These results indicate that HCV core protein has an oncogenic potential to transform the Rat-1 cell line but is not sufficient to either immortalize primary REFs by itself or transform primary cells in conjunction with the H-ras oncogene.
丙型肝炎病毒（HCV）的持续感染与肝硬化和肝细胞癌的发生有关。为了检测HCV核心基因产物的致癌潜力，在有或无H-ras癌基因存在的情况下，用核心基因转染原代大鼠胚胎成纤维细胞（REFs）。与之前的一份报告（R. B. Ray、L. M. Lagging、K. Meyer和R. Ray，《病毒学杂志》70:4438 - 4443，1996年）相反，尽管转染后20天核心蛋白成功表达，但未发现来自两种不同基因型（1a型和1b型）的HCV核心蛋白与H-ras癌基因协同作用将REFs转化为致瘤表型。此外，用G418筛选时，转染E1A而非表达核心蛋白质粒的REFs表现出永生化细胞的表型。通过观察来自劳斯肉瘤病毒长末端重复序列和猿猴病毒40启动子这两个病毒启动子的转录激活来证实其生物学活性，已知这两个启动子可被HCV - 1分离株的核心蛋白激活。与原代细胞的结果相反，稳定表达HCV核心蛋白的Rat - 1细胞系在裸鼠中表现出集落形成、不依赖贴壁生长和肿瘤形成。HCV核心蛋白能够以不同效率诱导Rat - 1细胞转化，这取决于核心蛋白的表达水平。这些结果表明，HCV核心蛋白具有转化Rat - 1细胞系的致癌潜力，但不足以单独使原代REFs永生化或与H-ras癌基因共同转化原代细胞。
