| Project/Area Number |
18K09255
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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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| Review Section |
Basic Section 56040:Obstetrics and gynecology-related
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| Research Institution | Shinshu University |
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Principal Investigator |
UCHIKAWA Junko 信州大学, 医学部, 助教(特定雇用) (00722927)
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| Co-Investigator(Kenkyū-buntansha) |
塩沢 丹里 信州大学, 学術研究院医学系, 教授 (20235493)
竹内 穂高 信州大学, 医学部附属病院, 助教(診療) (30816351)
宮本 強 信州大学, 学術研究院医学系, 准教授 (70418721)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | ARID1A / 子宮内膜癌 / 子宮内膜症 / 薬剤感受性 / マウスモデル / 異所性子宮内膜 / Arid1a |
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| Outline of Final Research Achievements |
We have established a mouse model capable of inducing gene knockout (KO) specifically in the endometrial epithelium. In this mouse model, Arid1a-KO did not change its phenotype, Pten-KO developed atypical hyperplasia after one week, and half of them became adenocarcinoma in about 6 to 8 weeks. In the double-KO of Arid1a and Pten, all cases became adenocarcinoma within ten days. Using this double-KO endometrial carcinoma mouse model, we examined the sensitivity of several drugs, including cisplatin, HDAC inhibitor/medroxyprogesterone acetate combination therapy, Niraparib, compound A, natural compound B. However, none of them were effective. We also established a mouse model that develops endometriotic cysts in the abdominal cavity of mice and succeeded in inducing carcinoma by inducing double-KO.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によりARID1A機能欠失がAEHからEECへの進行を促進することが明らかとなった。EEC発癌マウスモデルは今後の薬物療法検討に役立つと考えられる。また、同様に子宮内膜症発癌マウスモデルは、子宮内膜症発癌研究や薬物療法研究に役立つ可能性が考えられる。
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