The functional analysis of the nuclear receptor coactivator-6 (Ncoa6) which may modulate the estrogen sensitivity in the human endometrium and involves in the development of endometrial cancer.
| Project/Area Number |
16K11128
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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 |
Obstetrics and gynecology
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| Research Institution | Yamagata University |
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Principal Investigator |
Kawagoe Jun 山形大学, 医学部, 講師 (60375342)
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| Co-Investigator(Kenkyū-buntansha) |
永瀬 智 山形大学, 医学部, 教授 (00292326)
清野 学 山形大学, 医学部, 助教 (40594320)
太田 剛 山形大学, 医学部, 講師 (50375341)
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| Research Collaborator |
WATANABE Norikazu
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 脱落膜化 / 子宮体癌 / 子宮内膜 / 転写補助因子 / Ncoa6 / 核内受容体転写補助因子 / エストロゲン受容体 / エストロゲン / 婦人科腫瘍学 / 分子生物学 / 生殖内分泌学 |
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| Outline of Final Research Achievements |
We revealed that the strong expression of nuclear receptor coactivator-6 (Ncoa6) in both epithelial cells and stromal cells of normal human endometrium by using immunohistochemistry (IHC). Moreover, in the endometrioid adenocarcinoma of human endometrial cancer, we found that the expression of Ncoa6 was decreased or lost in some cases and there was negative correlation between tumor grade and strength of Ncoa6 expression (more grade, less Ncoa6 expression).
Then, we also investigated the function of Ncoa6 on in vitro decidualization of human endometrial stromal cells (HESCs) using primary culture of HESCs. We found that the suppression of Ncoa6 expression using siRNA technology resulted in the failure of morphological decidual change of HESCs after in vitro decidualization stimuli. Then, we also found that Ncoa6 regulates the expression of some genes involving in the actin binding and regulates the actin distribution during decidualization.
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| Academic Significance and Societal Importance of the Research Achievements |
先行研究において、マウスではNcoa6が子宮内膜におけるエストロゲン受容体の転写活性調節と発現抑制を介したエストロゲン感受性調節に重要な機能を持ち、内膜の脱落膜化や胚着床に対して重要な機能を持つことが報告されていた。しかし、ヒト子宮内膜におけるNcoa6の機能に関しては全く報告がなく、今回の我々の研究は、その点においで初めての研究報告となる。我々は、Ncoa6の発現が子宮内膜の機能にとって重要であることを示し、その発現低下が類内膜腺癌の悪性度と関連し、また、脱落膜化障害を引き起こすことを明らかにした。これは、Ncoa6が妊娠成立と将来的な内膜癌発症抑制に重要な因子であることを示した。
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Report
(4 results)
Research Products
(2 results)
