Mechanism of castration-resistance in prostate cancer via intratumoral steroidogenesis

2015 Fiscal Year Final Research Report

• 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
• Keywords: ACSL3 / 去勢抵抗性前立腺がん / 脂質代謝酵素

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.

Free Research Field

腫瘍学