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2004 Fiscal Year Final Research Report Summary

Analysis of HPV regulatory gene function with organotypic culture of epithelial cells.

Research Project

Project/Area Number 13214048
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKyoto University

Principal Investigator

SAKAI Hiroyuki  Kyoto University, Institute for Virus Research, Associate Professor, ウイルス研究所, 助教授 (80281731)

Project Period (FY) 2001 – 2004
KeywordsHPV / tumor virus / virus replication / viral oncology / hyperplasia
Research Abstract

There are many cancers associated with the infection of human papillomavirus (HPV), among which cervical cancer is considered the most important one. To prevent the HPV-induced cancer development, it is essential to understand the replication cycle of HPV on the molecular basis. However, the analysis of HPV life-cycle has been hampered by a fact that the HPV replication strongly depends on the differentiation program of epithelial cells. We developed an HPV replication system with organotypic culture of keratinocyte (raft culture) and a novel HPV replicon, which enable us to analyze the HPV replication and the HPV-induced hyperplasia in vitro.
With this system, we could obtain following results: (1) the efficient replication system of HPV could be adapted to the screening of anti-virus drugs, (2) activation of Ha-ras pathway conferred a malignant cell phenotype on the HPV-infected cells, (3) high-risk type E7 was responsible for the hyperplasia induction by HPV, in which the inactivation of both pRb and pl30 and the activation of JNK pathway might be involved, (4) continuous expression of E7 in the HPV-positive cervical cancer cell was essential for the cell viability and for the prevention of senescence induction, (5) E4 gene product could induce G2/M arrest in cell division cycle without preventing cellular DNA synthesis, suggesting the involvement of E4 in the viral DNA amplification in the differentiated layer of epidermis.

  • Research Products

    (13 results)

All 2003 2002 2001 2000

All Journal Article (13 results)

  • [Journal Article] Downregulation of CD4 is required for maintenance of viral infectivity of HIV-1.2003

    • Author(s)
      田中 正和 他
    • Journal Title

      Virology 311

      Pages: 316-325

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Downregulation of CD4 is required for maintenance of viral infectivity of HIV-1.2003

    • Author(s)
      Tanaka, M., Ueno, T.Nakahara, T., Sasaki, K., Ishimoto, A., Sakai, H.
    • Journal Title

      Virology 311

      Pages: 316-325

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Modulation of the cell division cycle by HPV18 E4.2002

    • Author(s)
      中原 知美 他
    • Journal Title

      Journal of Virology 76

      Pages: 10914-10920

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Modulation of the cell division cycle by HPV18 E4.2002

    • Author(s)
      Nakahara, T.Nishimura, A., Tanaka, M., Ueno, T., Ishimoto, A., Sakai, H.
    • Journal Title

      J.Virol. 76

      Pages: 10914-10920

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Analysis of dominant-negative effects of mutant Env proteins of human immunodeficiency virus type 1.2001

    • Author(s)
      岩谷 靖雅 他
    • Journal Title

      Virology 286

      Pages: 45-53

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Analysis of dominant-negative effects of mutant Env proteins of human immunodeficiency virus type 1.2001

    • Author(s)
      Iwatani, Y., Kawano, K., Ueno, T., Tanaka, M., Ishimoto, A., Ito, M., Sakai, H.
    • Journal Title

      Virology 286

      Pages: 453-53

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Modification of virus infectivity by cytoplasmic tail of HIV-1 TM protein.2001

    • Author(s)
      Iwatani, Y., Ueno, T., Nishimura, A., Zhang, X., Hattori, T., Ishimoto, A., Ito, M., Sakai, H.
    • Journal Title

      Virus Res. 74

      Pages: 75-87

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Mechanisms of human papillomavirus E2 mediated repression of viral oncogene expression and cervical cancer cell growth inhibition.2000

    • Author(s)
      西村 聡子 他
    • Journal Title

      Journal of Virology 74

      Pages: 3752-3760

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Resistance to friend murine leukemia virus infection conferred by the Fv-4 gene is recessive but appears dominant from the effect of the immune system.2000

    • Author(s)
      張 鳳民 他
    • Journal Title

      Journal of Virology 74

      Pages: 6193-6197

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Functional association between the nef gene product and gag-pol region of HIV-1.2000

    • Author(s)
      小野 岳史 他
    • Journal Title

      FEBS Letters 466

      Pages: 233-238

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Mechanisms of human papillomavirus E2 mediated repression of viral oncogene expression and cervical cancer cell growth inhibition.2000

    • Author(s)
      Nishimura, A., Ono, T., Ishimoto, A., Dowhanick, J.J., Frizzell, M.A., Howley, P.M., Sakai, H.
    • Journal Title

      J.Virol. 74

      Pages: 3752-3760

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Resistance to friend murine leukemia virus infection conferred by the Fv-4 gene is recessive but appears dominant from the effect of the immune system.2000

    • Author(s)
      Zhang, F., Ya, L.T., Iwatani, Y., Higo, K., Suzuki, Y., Tanaka, M., Nakahara, T., Ono, T., Sakai, H., Kuribayashi, K., Ishimoto, A.
    • Journal Title

      J.Virol. 74

      Pages: 6193-6197

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Functional association between the nef gene product and gag-pol region of HIV-1.2000

    • Author(s)
      Ono, T., Iwatani, Y., Nishimura, A., Ishimoto, A, Sakai, H.
    • Journal Title

      FEBS Letters 466

      Pages: 233-238

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2008-05-27  

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