The control of castration resistant prostate cancer (CRPC) through degradation of androgen receptor splice variant by dioxins

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11117
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Hokkaido University
• Principal Investigator: Maruyama Satoru 北海道大学, 医学研究院, 客員研究員 (80507591)
• Co-Investigator(Kenkyū-buntansha): 篠原 信雄 北海道大学, 医学研究院, 教授 (90250422)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 前立腺癌 / ダイオキシン受容体 / 芳香族炭化水素受容体 / アンドロゲン受容体 / Indirubin

Outline of Final Research Achievements

1.We produced AR splicing variant (AR-V7) to the prostate cancer strain which developed AhR to see the transcription activity of the androgen receptor and made expression cells for the purpose of examining in vitro transcription activity and proliferation potency on various conditions. However, there is a problem of vector, and the degree of the expression is feeble and is the situation that is thought to be unsuitable for an experiment, and makes trial and error. Thus, as in vivo examination, transplant (xenograft) to an immunodeficiency mouse is the state that is impossible of enforcement, too.
2.We did the endogenous dioxin mentioned above every dose as administration (toxic confirmation, estimate of the fatal dose) to a mouse of endogenous dioxin with the oral and transperitoneal plan that we gave it and observed day after day. However, it became non-enforcement by a problem of the when and where.

Free Research Field

泌尿器悪性腫瘍

Academic Significance and Societal Importance of the Research Achievements

これまでの前立腺癌に対する内分泌治療のホルモン分泌・増殖経路における作用部位はアンドロゲン受容体(AR)より上流でのシグナルを抑制するものであったが、より下流であるARを分解することは、いかに上流からのシグナル変化があろうと治療効果を持続また増強する可能性を秘めている。近年、本邦でも増加している前立腺ホルモン非依存性癌（去勢抵抗性前立腺癌）における新たな治療法に結びつく礎となることが期待される。