Analysis of the suppressive action of vitamin D3 on prostate cancer via AR signaling.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K20163
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Teikyo University
• Principal Investigator: SUSA TAKAO 帝京大学, 医学部, 助教 (20445852)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 前立腺癌 / ビタミンD3 / AR / VDR

Outline of Final Research Achievements

Aim of this study is to reveal the molecular mechanism of the crosstalk between DHT and vitaminD3 (D3) signaling in LNCaP cells. As the result, we identified Metallothionein genes and HOXC genes as a common target of DHT and D3. Metallothionein genes were repressive target genes both of DHT and D3, interestingly, its D3 dependent regulation was mediated by not only VDR but also AR. On the other hands, DHT and D3 showed a opposite regulation of HOXC genes. DHT repressed HOXC genes expression while D3 stimulated them. Interestingly, we found that HOXC might inhibit AR function as preliminary results. In addition, these DHT dependent gene repressions were involving the DNA methylation of their regulatory regions. We speculate that the DNA methylation by DHT might be a cause of the crosstalk between D3 and AR in Metallothionein gene regulation observed in this study, and revealing these will be a novel finding.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

前立腺癌は男性で発症頻度の高い癌であり、更なる治療方針やその予防策の開発が望まれている。本研究では、以前よりその分子機序は未明であったが癌の予防効果があると考えられたビタミンD3が前立腺癌に示す抗増殖作用の分子機序の一端を明らかにした。metallothioneinやHOXCと言う標的遺伝子の存在を明らかにし、これらが細胞増殖やアンドロゲンシグナリングに与える影響を明らかにしつつある。今後、前立腺癌の新たな分子標的ともなりうる。またその転写制御にはDNAのメチル化を介した転写制御が想定され、学術的にも社会的にも本研究成果の意義を主張したい。