Knockdown of scavenger receptor class B type I reduces prostate specific antigen secretion and viability of prostate cancer cells

Prostate. 2012 Jun 15;72(9):955-65. doi: 10.1002/pros.21499. Epub 2011 Oct 24.


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.

Publication types

  • Comparative Study

MeSH terms

  • Cell Line, Tumor
  • Cell Survival / genetics
  • Down-Regulation / genetics
  • Gene Knockdown Techniques*
  • Gene Silencing
  • Humans
  • Male
  • Prostate-Specific Antigen / antagonists & inhibitors*
  • Prostate-Specific Antigen / metabolism
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology*
  • Scavenger Receptors, Class B / biosynthesis
  • Scavenger Receptors, Class B / deficiency*
  • Scavenger Receptors, Class B / genetics*


  • SCARB1 protein, human
  • Scavenger Receptors, Class B
  • Prostate-Specific Antigen