Hepatitis B virus X antigen (HBxAg) and cell cycle control in chronic infection and hepatocarcinogenesis.
Hepatitis B and related viruses that infect mammalian hosts encode the "X" protein that has been shown to contribute importantly to the pathogenesis of chronic liver disease (CLD) and to the development of hepatocellular carcinoma (HCC). In a variety of tissue culture systems, hepatitis B virus (HBV) X antigen, or HBxAg, has been shown to trigger apoptosis, while other evidence suggests that HBxAg inhibits apoptosis and stimulates the cell cycle by constitutively activating a number of signaling pathways that are important for hepatocellular growth and survival. These apparently contrasting properties of HBxAg may be associated with differences in the X protein itself, since carboxy-terminal truncated forms of HBxAg appear to be associated with HCC lesions. Alternatively, or in addition, these differences may be due to the cell type, state of cell differentiation, and whether expression occurs in resting or dividing cells. Further, the association between HBxAg expression and chromosomal instability, may also contribute to the apparently contrasting fates of HBxAg positive cells. It is proposed that in many of these systems, the different outcomes of HBxAg expression may be due to the nature of the cellular response to HBxAg, and not due to differences in the fundamental properties of HBxAg, the latter of which promote cell survival, cell cycle progression, and the development of HCC.
Feitelson
Mark Alan
MA
Department of Pathology, Anatomy and Cell Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA. Mark.Feitelson@jefferson.edu <Mark.Feitelson@jefferson.edu>
Reis
Helena M G P V
HM
Liu
Jie
J
Lian
Zhaorui
Z
Pan
Jingbo
J
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000821:virology; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D005544:Forecasting; D006515:Hepatitis B virus / Q000502:physiology*; D019694:Hepatitis B, Chronic; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000821:virology; D015398:Signal Transduction / Q000187:drug effects; D015534:Trans-Activators / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D054334:Viral Regulatory and Accessory Proteins
D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein