Analysis of HPV regulatory gene function with organotypic culture of epithelial cells.
| Project/Area Number |
13214048
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Kyoto University |
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Principal Investigator |
SAKAI Hiroyuki Kyoto University, Institute for Virus Research, Associate Professor, ウイルス研究所, 助教授 (80281731)
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| Project Period (FY) |
2001 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥34,300,000 (Direct Cost: ¥34,300,000)
Fiscal Year 2004: ¥7,900,000 (Direct Cost: ¥7,900,000)
Fiscal Year 2003: ¥8,700,000 (Direct Cost: ¥8,700,000)
Fiscal Year 2002: ¥9,000,000 (Direct Cost: ¥9,000,000)
Fiscal Year 2001: ¥8,700,000 (Direct Cost: ¥8,700,000)
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| Keywords | HPV / tumor virus / virus replication / viral oncology / hyperplasia / パピローマウイルス / がん遺伝子 / 上皮組織 / 細胞分化 / 癌抑制遺伝子 / テロメレース / 細胞周期 |
|---|
| 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.
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Report
(5 results)
Research Products
(18 results)
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[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.
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Journal Title
Virology 311
Pages: 316-325
Description
「研究成果報告書概要(欧文)」より
Related Report
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[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.
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Journal Title
J.Virol. 76
Pages: 10914-10920
Description
「研究成果報告書概要(欧文)」より
Related Report
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[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.
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Journal Title
Virology 286
Pages: 453-53
Description
「研究成果報告書概要(欧文)」より
Related Report
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[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.
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Journal Title
Virus Res. 74
Pages: 75-87
Description
「研究成果報告書概要(欧文)」より
Related Report
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[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.
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Journal Title
J.Virol. 74
Pages: 3752-3760
Description
「研究成果報告書概要(欧文)」より
Related Report
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[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.
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Journal Title
J.Virol. 74
Pages: 6193-6197
Description
「研究成果報告書概要(欧文)」より
Related Report
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