| Project/Area Number |
17K08626
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
横田 崇 金沢大学, 医学系, 協力研究員 (50134622)
上田 篤 金沢大学, 医学系, 助教 (90728560)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 多能性幹細胞 / がん遺伝子 / 転写因子 / 遺伝子発現 / ES細胞 / ＥＳ細胞 / 自己複製 / 多分化能 |
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| Outline of Final Research Achievements |
Pluripotent stem cells, including mouse embryonic stem cells (ES cells) have self-renewal ability and pluripotency. The self-renewal ability of mouse ES cells is maintained by stimulation with the cytokine LIF followed by activation of the transcription factor STAT3. Several investigators, including us, have been working to elucidate the molecular basis of the self-renewal mechanism using STAT3 and its related transcription factors. Interestingly, it has been pointed out that ES cells have similarities with cancer cells. Recent studies have also reported various mutant STAT3 in human cancer tissues. In this study, we focus on the mutant STAT3 which is found in cancer cells and aims to elucidate a novel mechanism(s) of self-renewal regulation mediated by oncogenes.
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| Academic Significance and Societal Importance of the Research Achievements |
変異型STAT3をES細胞に過剰発現させると、LIF非依存的な自己複製が観察された。これらの細胞はLIF非存在下でアルカリフォスファターゼ陽性で、未分化マーカー遺伝子の発現も認められた。変異型STAT3の機能は、STAT3遺伝子破壊ES細胞でも観察できた。さらに興味深いことに、変異型STAT3はLIF非存在下でES細胞の増殖能を促進する機能があることを見出した。このことから、変異型STAT3はLIFに依存することなく、ES細胞の自己複製を維持する機能が示された。これは、がん細胞で認められる遺伝子発現制御機構をES細胞内で再構築することで、ES細胞の幹細胞性を模倣できている可能性を示唆する。
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