Transcriptional regulatory mechanisms involving epigenomic modifications that define the antiproliferative effects of Vitamin D3 on prostate cancer.

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K09699
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Teikyo University
• Principal Investigator: SUSA TAKAO 帝京大学, 医学部, 講師 (20445852)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 前立腺がん / ビタミンD / アンドロゲン

Outline of Final Research Achievements

The current investigation revealed the regulatory mechanism governing the expression of the transcriptional factor HOXC9, elucidating its involvement in the androgen-induced proliferation of human prostate cancer LNCaP cells, as well as its contribution to the anti-proliferative effect of Vitamin D3. HOXC9 was found to undergo transcriptional repression through DNA methylation in an androgen-dependent manner. Multiple analyses conducted using HOXC9 stable LNCaP cells, which maintained HOXC9 expression under androgen administration, demonstrated the interaction between HOXC9 and androgen-activated AR transcriptional complexes, leading to the inhibition of AR binding to its target DNA sequences. In essence, the down regulation of HOXC9 in prostate cancer is believed to maintain an intracellular environment conducive to androgen-dependent proliferation, while vitamin D3 induces HOXC9 expression to inhibit androgen activity, contributing to its anti-proliferative effect on prostate cancer.

Free Research Field

内分泌学

Academic Significance and Societal Importance of the Research Achievements

厚生労働省による令和２年の人口動態統計調査では、前立腺がんの死亡者数は12759人であり、これはがん全体の第6位にあたる。高齢化社会が進む近年、加齢に伴って罹患率が上昇する前立腺がんの患者数は増加の一途を辿っている。前立腺がんの治療には抗アンドロゲン薬など複数の薬が開発されているが、それらに抵抗性を示す抵抗性がんの出現が問題となっており、さらなる前立腺がんの新規治療戦略の開発が求められているのが現状と言える。その点、本研究で得られた研究成果は、既存の治療薬とは異なるメカニズムでARを阻害するものであり、新規治療戦略の候補と言えるものであり、本研究には学術的・社会的意義があるものと言える。