Mechanism of castration-resistance in prostate cancer via intratumoral steroidogenesis

Research Project

Project/Area Number	24590474
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Experimental pathology
Research Institution	Japanese Foundation for Cancer Research (2014-2015) Tokyo Metropolitan Institute of Medical Science (2013) The University of Tokyo (2012)
Principal Investigator	Migita Toshiro 公益財団法人がん研究会, その他部局等, 研究員 (20462236)
Project Period (FY)	2012-04-01 – 2016-03-31
Project Status	Completed (Fiscal Year 2015)
Budget Amount *help	¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000) Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords	ACSL3 / 去勢抵抗性前立腺がん / 脂質代謝酵素 / 前立腺がん / ステロイド合成 / ステロイド代謝 / 脂質代謝 / アンドロゲン代謝
Outline of Final Research Achievements	Long-chain acyl-conzyme A (CoA) synthetase 3 (ACSL3) is one of de novo lipogenic enzymes, and is involved in diverse cellular processes as well as lipid droplet formation. ACSL3 overexpression or suppression modulated the expression of enzymes that stimulates the testosterone synthesis from adrenal androgen. Castration-resistant prostate cancer (LTAD) cells had high levels of both ACSL3 and the steroidogenic enzymes. Stimulation by exogenous adrenal androgen increased levels of intracellular testosterone and dihydrotestosterone (DHT) in LTAD cells, associated with a significant increase in cell growth. These findings suggest that ACSL3 contributes to castration-resistant growth of prostate cancer through maintaining intratumoral androgen levels by stimulating androgen synthesis from adrenal androgen.