The loss of Arid1a function on endometrial carcinogenesis and drug sensitivity

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09255
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Shinshu University
• Principal Investigator: UCHIKAWA Junko 信州大学, 医学部, 助教(特定雇用) (00722927)
• 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)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: ARID1A / 子宮内膜癌 / 子宮内膜症 / 薬剤感受性 / マウスモデル

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.

Free Research Field

産婦人科学

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。