Knockdown of scavenger receptor Class B Type I reduces prostate specific antigen secretion and viability of prostate cancer cells

Citations Over Time

Abstract

Abstract BACKGROUND Scavenger Receptor Class B Type I (SR‐BI) facilitates influx of cholesterol to the cell from lipoproteins in the circulation. This influx of cholesterol may be important for many cellular functions, including synthesis of androgens. Castration‐resistant prostate cancer tumors are able to synthesize androgens de novo in order to supplement the loss of exogenous sources often induced by androgen deprivation therapy. Silencing of SR‐BI may impact the ability of prostate cancer cells, particularly those of castration‐resistant state, to maintain the intracellular supply of androgens by removing a supply of cholesterol. METHODS SR‐BI expression was knocked down using small interfering RNA in LNCaP and C4‐2 cells. The effect of down‐regulation of SR‐BI on PSA production, cell toxicity, and cell viability was measured in both cell types. In addition, compensatory cholesterol synthesis activity was measured using the radiolabeled precursor, 14 C‐acetate. RESULTS SR‐BI protein expression is higher basally in C4‐2 cells than LNCaP cells. Silencing of SR‐BI expression to greater than 85% reduced PSA production in LNCaP and C4‐2 SRBI‐KD cells by 55% and 58% compared to negative control cells, respectively. SR‐BI‐KD C4‐2 cells demonstrated significantly reduced cell viability (>25%) compared the NC cells. CONCLUSIONS The down‐regulation of SR‐BI significantly impacts PSA production of prostate cancer cells, as well as the viability of C4‐2 cells in the presence and absence of HDL. This may indicate a deficiency in cholesterol availability to the androgen synthesis pathway or may implicate a role for SR‐BI in prostate cancer signal transduction pathways. Prostate 72:955–965, 2012. © 2011 Wiley Periodicals, Inc.

Related Papers

• Androgen receptor stabilization in recurrent prostate cancer is associated with hypersensitivity to low androgen.(2001)
• → Switch from antagonist to agonist of the androgen receptor blocker bicalutamide is associated with prostate tumour progression in a new model system(1999)420 cited
• → p-Carborane-based androgen antagonists active in LNCaP cells with a mutated androgen receptor(2011)27 cited
• → Abstract 3930: Ligand-independent activity of the mutant LNCaP androgen receptor drives cell proliferation in hormone-independent LNCaP tumor cells(2012)1 cited
• Cell growth promoting of the androgen receptor mutation(2006)