Hepatitis B virus X protein overcomes oncogenic RAS-induced senescence in human immortalized cells Hepatitis B virus X protein overcomes oncogenic RAS-induced senescence in human immortalized cells

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Author(s)

    • OISHI Naoki
    • Department of Signal Transduction, Cancer Research Institute, Graduate School of Medicine, Kanazawa University
    • SHILAGARDI Khurts
    • Department of Signal Transduction, Cancer Research Institute, Graduate School of Medicine, Kanazawa University
    • NAKAMOTO Yasunari
    • Department of Disease Control and Homeostasis, Graduate School of Medicine, Kanazawa University
    • HONDA Masao
    • Department of Disease Control and Homeostasis, Graduate School of Medicine, Kanazawa University
    • KANEKO Shuichi
    • Department of Disease Control and Homeostasis, Graduate School of Medicine, Kanazawa University
    • MURAKAMI Seishi
    • Department of Signal Transduction, Cancer Research Institute, Graduate School of Medicine, Kanazawa University

Abstract

医薬保健研究域医学系Chronic infection with hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma. The HBV X protein (HBx) is thought to have oncogenic potential, although the molecular mechanism remains obscure. Pathological roles of HBx in the carcinogenic process have been examined using rodent systems and no report is available on the oncogenic roles of HBx in human cells in vitro. We therefore examined the effect of HBx on immortalization and transformation in human primary cells. We found that HBx could overcome active RAS-induced senescence in human immortalized cells and that these cells could form colonies in soft agar and tumors in nude mice. HBx alone, however, could contribute to neither immortalization nor transformation of these cells. In a population doubling analysis, an N-terminal truncated mutant of HBx, HBx-D1 (amino acids 51-154), which harbors the coactivation domain, could overcome active RAS-induced cellular senescence, but these cells failed to exhibit colonigenic and tumorigenic abilities, probably due to the low expression level of the protein. By scanning a HBx expression library of the clustered-alanine substitution mutants, the N-terminal domain was found to be critical for overcoming active RAS-induced senescence by stabilizing full-length HBx. These results strongly suggest that HBx can contribute to carcinogenesis by overcoming active oncogene-induced senescence. © 2007 Japanese Cancer Association.

Journal

  • Cancer Science

    Cancer Science 98(10), 1540-1548, 2007-10-10

    Japanese Cancer Association / Blackwell Publishing Ltd

References:  43

Codes

  • NII Article ID (NAID)
    10019997274
  • NII NACSIS-CAT ID (NCID)
    AA11808050
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    13479032
  • Data Source
    CJP  IR 
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