2020 Fiscal Year Final Research Report
Elucidation of estrogen-related receptor signaling pathway by using CRISPR/Cas9 in endometrial cancer
| Project/Area Number |
19K24034
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0906:Surgery related to the biological and sensory functions and related fields
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
KOKABU TETSUYA 京都府立医科大学, 女性生涯医科学, 助教 (80848490)
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| Project Period (FY) |
2019-08-30 – 2021-03-31
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| Keywords | 子宮体癌 / endometrial cancer / estrogen / chemoresistance / estrogen receptor / ER / ERRα |
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| Outline of Final Research Achievements |
We previously reported that estrogen-related receptor α (ERRα) regulated tumor progression in endometrial cancer. Recent studies revealed that ERRα also regulated resistance of cancer cells to chemotherapy in various cancers. Therefore, we evaluated the association between ERRα and chemo-resistance in endometrial cancer. Chemo-resistant endometrial cancer cell (CREC) models were developed in our laboratory. ERRα expression was edited by using CRISPR/Cas9 and small interfering RNA.
WST-8 assay revealed CRECs were resistant to plural anticancer agents. RT-PCR and western blotting showed increased levels of ERRα, MDR1, XIAP, and Bcl-2 in CRCEs. Additionally, CRCEs also presented decreased level of miR9, which was involved in ERRα regulated mRNA stability of MDR1. On the other hand, knockdown of ERRα induced down-regulation of MDR1 expression via up-regulation of miR9 expression. Therefore, these findings suggested that ERRα regulated chemo-resistance in endometrial cancer.
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| Free Research Field |
子宮体癌
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| Academic Significance and Societal Importance of the Research Achievements |
本邦の子宮体癌患者は急激に増加しているが、予後不良な進行・再発例や妊孕能温存が必要な若年例における治療成績は十分とは言えない。本研究は子宮体癌の腫瘍学的特徴であるホルモン依存性疾患に着目し、エストロゲン伝達系制御による包括的な治療を目標としている。
我々はエストロゲン関連受容体（ERRα）が子宮体癌において予後因子であること、腫瘍進行を制御することを示した。また化学療法抵抗性獲得に密接に関与することを示し、これらの結果は従来の治療法と異なった作用機序による腫瘍制御を可能としており、ERRαが子宮体癌における新規治療戦略における有用な標的となり得ると考えられる。
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