FP06-3 Steroidogenic Factor 1 Drives Aggressive Prostate Cancer Cell Proliferation and Plays a Critical Role in Tumor Growth

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 381-386-Steroid Hormone Actions, Biosynthesis & Metabolism
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-384
Samantha Rose Lewis*1, William Allen Ricke2 and Joan Susan Jorgensen3
1University of Wisconsin-Madison, Madison, WI, 2University of Wisconsin, Madison, WI, 3Univ of Wisconsin, Madison, WI
The dependence of prostate cancer on androgens provides a targeted means of treating advanced disease. Unfortunately, androgen deprivation therapies that block gonadal steroid synthesis ultimately become ineffective, leading to the deadly form of prostate cancer. While there are likely many ways this transition to treatment refractive cancer can occur, one important factor is the ability of prostate adenocarcinoma cells to acquire machinery for de novo steroidogenesis and therefore, fuel their own growth. The mechanisms by which prostate cancer cells initiate and maintain steroidogenesis are unknown. We hypothesize that Steroidogenic Factor 1 (NR5A1, ADBP4, SF1), a key regulator of steroidogenesis in normal endocrine tissues, is expressed in castration resistant prostate cancer where it stimulates aberrant steroidogenesis and fuels malignant growth. Notably, SF1 is not expressed in normal prostate tissue. Our results indicated that SF1 was absent in benign prostate cell lines as expected, but present in aggressive prostate cancer cell lines. When ectopic SF1 expression was induced in benign prostate epithelial cells (BPH1), increased steroidogenic enzyme expression, steroid synthesis, and cell growth was observed. Converse experiments using shRNA-mediated knockdown of SF1 in an aggressive prostate cancer cell line (WR3) diminished steroidogenic activity and inhibited cell growth. SF1 depleted cells also exhibited signs of decreased cell cycle progression and defects in cell division. Xenograft studies were performed to evaluate the role of SF1 in tumor growth. Results comparing control versus SF1 deficient prostate cancer cells showed that knockdown of SF1 substantially impaired tumor growth under the kidney capsule in both castrated and intact nude mouse hosts. Based on these data, we conclude that aberrant SF1 expression in aggressive prostate cancers stimulates steroidogenesis and promotes aggressive tumor growth. These findings present a new potential mechanism and therapeutic target for deadly castration resistant prostate cancer.

Nothing to Disclose: SRL, WAR, JSJ

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm