Infection of HepG2 cells with recombinant adenovirus encoding the HCV core protein induces p21WAF1 down-regulation – effect of transforming growth factor β

Background/Aims: Chronic infection with hepatitis C virus leads to liver cirrhosis and hepatocellular carcinoma. Hepatocellular carcinoma is sometimes associated with p53 dysfunction and decreased p21WAF1 expression. The p21WAF1 gene is a major target of p53, and p21WAF1 protein regulates the activities of cyclin/CDK complexes involved in cell cycle control and tumor formation. Because core protein has oncogenic properties, we investigated the expression of p21WAF1 following core expression. Methods: We analyzed by Western blot, Northern blot and transfection the expression of p21WAF1 in HepG2 cell line under transient expression of Hepatitis C core protein by recombinant-adenoviral infection. Results and discussion: Infection of HepG2 with core-encoding viruses induced the down-regulation of p21WAF1 expression. This effect is due to a decrease in the p21WAF1 gene transcription and of the p21WAF1 protein half-life. These results support a role for Hepatitis C virus core protein in cell transformation. We also found also that the transforming growth factor β can counteract the core-induced p21WAF1 down-regulation. The antagonist effect of TGF β, or of other molecules, on p21WAF1 expression may be of particular interest for the treatment of HCV-positive hepatocellular carcinoma.