title: Molecular pathogenesis of human hepatocellular carcinoma.
abstract: Primary hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, the viral-chemical etiology as well as molecular mechanisms of HCC pathogenesis remains largely unknown. Recent studies in our laboratory have identified several potential factors that may contribute to the pathogenesis of HCC. Oxidative stress and chronic inflammation have been linked to an increased risk of liver cancer. For example, oxyradical overload diseases such as Wilson disease and hemochromatosis result in the generation of oxygen/nitrogen species that can cause mutations in the p53 tumor suppressor gene. The Hepatitis B virus X gene (HBx), a viral transactivator with oncogenic potentials, has been shown to bind to and inactivate p53-mediated apoptosis. HBx mutants derived from HCC have a diminished ability to act as a transactivator. However, they still retain the ability to bind to and abrogate p53-mediated apoptosis. The comparison of gene expression profiles between HBx-expressing primary human hepatocytes and HBV-infected liver samples by cDNA microarrays indicate a unique alteration of a subset of oncogenes and tumor suppressor genes including p53. Our studies implicate both viral and endogenous chemical processes in the etiology of HCC, and p53 may be a common target for the inactivation during liver carcinogenesis.
authors.affiliation: Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. xin_wei_wang@nih.gov
authors.forename: Xin W
authors.initials: XW
authors.lastname: Wang
authors.forename: S Perwez
authors.initials: SP
authors.lastname: Hussain
authors.forename: Teh-Ia
authors.initials: TI
authors.lastname: Huo
authors.forename: Chuan-Ging
authors.initials: CG
authors.lastname: Wu
authors.forename: Marshonna
authors.initials: M
authors.lastname: Forgues
authors.forename: Lorne J
authors.initials: LJ
authors.lastname: Hofseth
authors.forename: Christian
authors.initials: C
authors.lastname: Brechot
authors.forename: Curtis C
authors.initials: CC
authors.lastname: Harris
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology / Q000821:virology; D016158:Genes, p53 / Q000235:genetics; D006525:Hepatitis, Viral, Human / Q000150:complications / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D009154:Mutation / Q000235:genetics