Modulation of p53-induced cell cycle progression, DNA repair and apoptosis by HCV gene expression.

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The role of p53 and HCV gene expresssion on cell cycle progression, apoptosis, and DNA reapir was investigated. Anticancer drugs such as etoposide and mitomycin C induced apoptosis in human PLC/PRF/5 hepatoma cells. Nuclear accumulation of p53 was observed preceeding the apoptosis. To investigate the role of p53, we introduced p53 gene into a retroviral expression vecotr pZIP,and the retrovirus carryiing p53 gene was produced. The growth of hepatoma cells in vivo and in vivo was inhihibed by the transfer of wild-type p53 gene.An antiangiogenic compound TNP470, a derivative of Fumagillin, induced apoptosis in both hepatoma cells and vascular endothelial cells and suppressed the in vivo growth of hepatoma cells. p53 acted additively with this anti-angiogenic compound. Apoptosis of the hepatoma cells appeared to be regulated by ras-PI-3-kinase pathway and NF-kB.Both TNP470 and p53 was suggested to be playing important role in modulating these pathways and inducining apoptosis.In order to analyze the effects of HCV gene expression, the viral gene fragments were introduced into the retroviral expression vector. The analysis on the effects of expression on these genes on ras-PI-3kinase and NF-kB is known in progress.