| Project/Area Number |
17K17831
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Environmental physiology(including physical medicine and nutritional physiology)
Tumor biology
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| Research Institution | Kansai Medical University (2018)
Kyoto University (2017) |
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Principal Investigator |
MIKI Takao 関西医科大学, 医学部, 講師 (30452345)
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| Research Collaborator |
Noda Makoto
Takahashi Chiaki
Shimba Shigeki
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | がん抑制遺伝子 / 概日リズム / RB / PER2 / ヘム / Rb / 代謝 |
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| Outline of Final Research Achievements |
Recent progress of molecularly targeted therapy suggests that finding of new connection between cancer and other pathway is beneficial to design new medicine. Epidemiological and clinical studies suggest that circadian clock disruption and the cancer progression are related. International Agency for Research on Cancer (IACR) classified shift work with circadian disruption as a group 2 human carcinogen. However, the molecular mechanism of how the circadian clock is disrupted in cancer and the consequence of circadian clock disruption in cancer are still unclear. Recently, our group has reported that mutation in p53 or PML in mice show deregulated circadian clock gene Period2 expression and disruption of the circadian rhythm, suggesting the close interplay between pathways for circadian clock and tumor suppression. We have identified previously unappreciated role of tumor suppressor in the mammalian circadian clock mechanism and cancer progression.
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| Academic Significance and Societal Importance of the Research Achievements |
がん抑制遺伝子産物Rbは、転写因子E2Fと結合してその作用を抑制することが知られている。しかし申請者は、Rbと概日リズムの関連から、Rbの全く新しい標的分子制御機構を見出した。この知見に基づく本研究は学術的に独自性が高いだけでなく、Rbによる新規の細胞周期、分化、代謝制御機構解明への道を切り開く可能性があり、非常に発展性が高いと考えられる。また、Rbの新規制御経路を標的とした薬剤は、がん及びリズム障害を伴う病気への適用が期待できる。
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