HEPATITIS-C VIRUS CORE PROTEIN COOPERATES WITH RAS AND TRANSFORMS PRIMARY RAT EMBRYO FIBROBLASTS TO TUMORIGENIC PHENOTYPE

We have previously demonstrated that hepatitis C virus (HCV) core prot ein regulates cellular proto-oncogenes at the transcriptional level; t his observation implicates core protein in the alteration of normal he patocyte growth. In the present study, the transforming potential of t he HCV core gene was investigated by using primary rat embryo fibrobla st (REF) cells which were transfected with or without cooperative onco genes, Integration of the HCV core gene resulted in expression of the viral protein in REF stable transformants. REF cells cotransfected wit h HCV core and H-ras genes became transformed and exhibited rapid prol iferation, anchor-independent growth, and tumor formation in athymic n ude mice, Results from these studies suggest that the core protein pla ys an important role in the regulation of HCV-infected cell growth and in the transformation to tumorigenic phenotype. These observations su ggest a possible mechanism for this viral protein in the pathogenesis of hepatocellular carcinoma in HCV-infected humans.