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 p21(WAF1) expression. The p21(WAF1) gene is a major target of p53, and p21(WAF1) 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 p21(WAF1) following core expression. Methods: We analyzed by Western blot, Northern blot and transfection the expression of p21(WAF1) 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 p21(WAF1) expression. This effect is due to a decrease in the p21(WAF1) gene transcription and of the p21(WAF1) 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 beta can counteract the core-induced p21(WAF1) down-regulation. The antagonist effect of TGF beta, or of other molecules, on p21(WAF1) expression may be of particular interest for the treatment of HCV-positive hepatocellular carcinoma. (C) 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.