The significance of androgen on refractory urothelial carcinoma of the urinary bladder as a therapeutic target

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K07420
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Tohoku Medical and Pharmaceutical University
• Principal Investigator: Nakamura Yasuhiro 東北医科薬科大学, 医学部, 教授 (80396499)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 膀胱尿路上皮癌 / アンドロゲン受容体 (AR) / PMEPA1 / EMT

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.

Free Research Field

人体病理学

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。