Development of diagnostic and therapeutic strategies for hormone therapy-resistant prostate cancer diagnosis and treatment using the canine AR complex as a origin.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06390
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Nippon Veterinary and Life Science University
• Principal Investigator: Ochiai Kazuhiko 日本獣医生命科学大学, 獣医学部, 准教授 (30550488)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: イヌ / 前立腺がん / アンドロゲン受容体

Outline of Final Research Achievements

Androgen receptor signaling (AR signaling)-independent prostate, which is refractory in humans, approximates canine hormone therapy-resistant prostate cancer pathology that occurs under castration conditions, and is of great significance in elucidating the mechanisms underlying the development and refractoriness of canine prostate cancer.
In order to elucidate the mechanism of canine AR signaling under androgen-independent conditions, the applicant has cloned the entire length of the canine AR and used it in various experiments. In this context, the effect of the number of glutamine (Q) repeats present in the canine AR on the AR signaling mechanism was examined from a cell biological perspective. The role of REIC/Dkk-2 and SGTA as regulators of this mechanism was also examined.

Free Research Field

獣医分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

イヌは去勢により雄性ホルモン分泌の遮断を行うにもかかわらず、雄性ホルモン誘導性の前立腺がんを発症する。このメカニズム解明はヒト前立腺がんのうち、ホルモン療法に抵抗性を示す難治性症例の病態解明に繋がることが期待される。本申請課題では、イヌのアンドロゲン受容体がもつ構造多型がアンドロゲン受容体シグナル伝達におよぼす影響について解析した。また、本機構に対する、がん抑制遺伝子REIC/Dkk-3およびコシャペロン分子であるSGTA分子の関与についても解析した。