| Project/Area Number |
10670295
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH, THE TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE |
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Principal Investigator |
KOHARA Kyoko THE TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE, Department of Microbiology and Cell Biology, Researcher, 東京都臨床医学総合研究所, 研究員 (20225478)
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| Co-Investigator(Kenkyū-buntansha) |
KOHARA Michio THE TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE, Department of Microbiology and Cell Biology, Researcher, 東京都臨床医学総合研究所, 研究員 (10250218)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | HCV / Cre / loxP expression system / HCV expressing cell line / HCV Tg mouse / Mechanism of Carcinogenesis / p21 / CIP1 / WAF1 / 腫瘍原性 |
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| Research Abstract |
Hepatitis C virus (HCV) infects persistently and causes chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). To address the effect of persistent infection, the conditional expression system of full-genome HCV in human liver cells was established. Following HCV expression, DNA synthesis of cells was suppressed, cell growth was mainly retarded at G0/G1 phase through apoptosis independent pathway. However, after 48 days passage, cell growth has been recovered to be initial level. In order to clarify the target of HCV, we examined the expression level of growth regulators. The cell growth modification by HCV correlated to the extent of p21WAF1/CIP1 expression and hyperphosphorylation of Rb was induced after 48 days passage. This modification of p21WAF1/CIP1 by HCV was caused at transcriptional level in the p53 independent manner. Thus, HCV could modify the cell cycle checkpoint to accelerate the tomurigenicity of hepatocyte through p21WA1/CIP1.
The effect of HCV in vivo was also characterized with HCV-transgenic mice model. Expression of HCV made hepatocytes more resistant to Fas-mediated apoptosis. By using in vitro and in vivo HCV expression model, we further characterized the molecular mechanism of pathogenesis of HCV.
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