Functional Analysis and Clinical Application of the Novel AR Signaling Pathway Regulator JMJD1C in Prostate Cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K18102
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Fukuokaya Wataru 東京慈恵会医科大学, 医学部, 助教 (30814975)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 前立腺癌 / JMJD1C / アンドロゲン受容体 / Beta-catenin

Outline of Final Research Achievements

This study aimed to elucidate the role of JMJD1C as a mechanism of treatment resistance in prostate cancer. As a result, it was confirmed that JMJD1C is uniformly expressed in both castration-sensitive and endocrine therapy-resistant prostate cancer cell lines. Correlations were observed between JMJD1C and the beta-catenin pathway, homologous recombination repair-related genes, and cell proliferation signal genes, suggesting that JMJD1C may be involved in the progression of prostate cancer through these pathways. JMJD1C expression showed a strong correlation with AR and AR-V7, indicating its involvement in treatment resistance via the androgen signaling pathway. The correlation with HIF1A was also revealed, demonstrating that JMJD1C plays a multifaceted role in the proliferation of prostate cancer.

Free Research Field

泌尿器腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究によりJMJD1Cが去勢感受性および内分泌療法抵抗性の前立腺癌細胞株で一様に発現していることが確認され、薬剤耐性に関与する分子としての重要性が示された。さらに、JMJD1Cはbeta-catenin経路やPI3K/Akt経路、HIF1A経路と関連しており、これらを介して前立腺癌の進行に寄与していることが判明した。特に、ARおよびAR-V7との強い相関が見られ、アンドロゲンシグナル経路を通じて治療抵抗性に関与していることが示唆された。これらの結果は、前立腺癌の新たな治療標的としてJMJD1Cの可能性を示し、臨床応用の基盤を提供するものである。