| Project/Area Number |
19K07420
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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 49020:Human pathology-related
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| Research Institution | Tohoku Medical and Pharmaceutical University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 膀胱尿路上皮癌 / アンドロゲン受容体 (AR) / PMEPA1 / EMT / アンドロゲン受容体(AR) / 難治性膀胱尿路上皮癌 / T24細胞 / NKB1細胞 / PTOV1 / T24細胞株 / NKB1]細胞 / アンドロゲン受容体 / 免疫組織化学的検討 / NKB1 / アンドロゲン / 治療標的 |
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| Outline of Research at the Start |
①難治性膀胱尿路上皮癌症例におけるアンドロゲン受容体(AR)、アンドロゲン合成/代謝酵素、アンドロゲン応答遺伝子、各種癌関連因子などの発現状況の解析を行う。
②上記症例でのAR遺伝子の増幅、変異、エピジェネティックな変化の有無の検索を行う。
③培養膀胱尿路上皮癌細胞でのアンドロゲンの機能的役割の検討を行う。
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| Outline of Final Research Achievements |
Immunohistochemical analysis revealed that AR expression was generally low in cases with muscle-infiltrating urothelial carcinoma of the urinary bladder as well as its metastatic lesion of the lymph node, but there were some cases of high expression levels of AR. In vitro study demonstrated that an increased expression levels of PMEPA1, known as an AR-related factor, was confirmed in T24 cells with the forced expression of AR compared to original T24 cells. In addition, the expression level of vimentin, an EMT marker, decreased in T24 cells with the forced expression of PMEPA1, and caspase-9 expression and proliferation decreased in T24 cells with the forced expression of AR-PMEPA1 by DHT in a dose-dependent manner, respectively. These results suggested that the association between AR, PMEPA1 and EMT could play pivotal roles in the pathogenesis of bladder cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、これまであまり関連性が提唱されてこなかった膀胱尿路上皮癌とアンドロゲンとの関係について、新知見を得ることが出来た。本研究成果により、アンドロゲンに着目した難治性膀胱尿路上皮癌の新たな診断バイオマーカーや治療方法の開発につながる可能性が期待できうるものと考えられる。
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