Knockdown of scavenger receptor class B type I reduces prostate specific antigen secretion and viability of prostate cancer cells.
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.
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Alexis L
AL
Twiddy
Michael E
ME
Cox
Kishor M
KM
Wasan
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D008297:Male; D017430:Prostate-Specific Antigen / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051122:Scavenger Receptors, Class B / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*
C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D017430:Prostate-Specific Antigen