The protooncogene c‐jun is transactivated by the X protein of hepatitis B virus and highly expressed in liver cancer

A specific viral oncogenic mechanism has not been shown for hepatitis B virus (HBV), although persistent HBV infection has been strongly associated with the development of hepatocellular carcinoma (HCC). Most HCC in HBV carriers contain integrated viral sequences in host DNA and this raises the question of whether such integrations ever contribute to oncogenesis. HBV contains a gene (designated the hbx gene), which encodes a transcriptional transactivator protein capable of activating homologous and heterologous cis?acting regulatory sequences. Among the regulatory sequences that are responsive to hbx are those of HBV and heterologous regulatory sequences in the long terminal repeat (LTR) of human immunodeficiency virus type 1 (HIV?1) and Rous sarcoma virus, and regulatory sequences of simian virus 40 and the human β interferon gene. The diversity of regulatory sequence that appear to be activated by hbx suggests that the hbx protein acts by a general mechanism that is not DNA sequence specific and other cellular genes may be similarly transactivated. This property of hbx raises the question of whether hbx expression in infected hepatocytes may activate cellular genes that could play a role in HCC, and hbx has been shown to be expressed from integrated viral genomic DNA in some HCC. In this regard, hbx was found to activate transcription regulated by the promoter of the protooncogene c?jun. c?jun was found to be expressed at a very low level in normal liver tissue but at high levels in HCC of HBV?infected patients. Copyright ? 1993, Wiley Blackwell. All rights reserved