2021 Fiscal Year Final Research Report

Elucidating mechanism regarding regulation of cell size through estrogen receptor alpha

Research Project

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Project/Area Number	19K09811
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	Tokyo Medical University
Principal Investigator	Li Zhong-Lian 東京医科大学, 医学部, 准教授 (80319532)
Co-Investigator(Kenkyū-buntansha)	伊藤正裕東京医科大学, 医学部, 主任教授 (00232471) 表原拓也東京医科大学, 医学部, 講師 (40800545) 永堀健太東京医科大学, 医学部, 助教 (50759561) 宮宗秀伸東京医科大学, 医学部, 講師 (80422252) 矢倉富子東京医科大学, 医学部, 講師 (20722581)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	Estrogen receptor alpha / Cell size / Cancer / Endometrium / Uterine / Subcellular
Outline of Final Research Achievements	The effects of estrogen on cells are mediated through the estrogen receptor α (ERα) which localizes at the peri-membrane, cytoplasm, and the nucleus of cells. To investigate how ERα plays its roles ERα-negative endometrial carcinoma cells (ERα-) were stably transfected with plasmid of human ERα carrying a substituted phenylalanine at position 445 with alanine (ERα-F445A), which was localized at the cytoplasm and nucleus. Treated with 17β-estrogen (E2) or bazedoxifene (BDF), the cell-size and expression of kinases related to ERα were observed. The cell cycle-related changes in cell-size were found in ERα-F445A cells, accompanied by the increase in mitochondrial membrane potential. The expression of mammalian target of Rapamycin (mTOR) phosphorylated at serine 2448 was decreased, which was recovered in presence of E2 in the ERα-F445A cells. The present results indicate that the cytonuclear ERα-F445A plays an important role in regulation of cell-size.
Free Research Field	産婦人科
Academic Significance and Societal Importance of the Research Achievements	子宮内膜細胞の細胞サイズ制御機構についてはこれまでにほとんど解明されていない。一方で近年、細胞サイズの制御にミトコンドリアの生合成が関係していることが報告された（Yamamoto, et al, 2014）。本研究は、細胞質と核内に局在するERαはリン酸化ｍTORとミトコンドリアを介して、細胞サイズの変化に関与することが示唆された。本研究課題の成果はこれまでに解明されなかった哺乳類の細胞サイズを制御するための分子基盤を明らかにする可能性がある。本課題により得られるデータは、医療現場における有用な基礎知見を深めながら診断・治療法の開発につながることが期待される。