HCV core protein modulates Rb pathway through pRb down-regulation and E2F-1 up-regulation

It has been recognized that the HCV (hepatitis C virus) core protein plays an important role in hepatocarcinogenesis. The functional inactivation of t he Rb pathway appears to be a major event for multi-step cancer carcinogene sis. To elucidate the role of the HCV core protein in hepatocarcinogenesis, we investigated the effect of the HCV core protein on the Rb pathway in bo th Rat-1 cell lines, stably expressing the HCV core protein and the doxycyc line-regulated cell lines. The HCV core stable transfectants showed a drama tic decrease ill the pRb levels and E2F-1 up-regulation. In the doxycycline -regulated cell lines, the PRb levels were significantly decreased which ar e followed by E2F-1 up-regulation. HCV core stable transfectants showed hig her cell growth rates and were sensitize to apoptosis. Thus, our results fi rst indicate that the HCV core protein decreases the expression of pRb, the reby allowing E2F-1 to be constitutively active, which is thought to result in rapid cell proliferation or sensitizing to apoptosis. (C) 2001 Elsevier Science B.V. All rights reserved.