Abstract B20: The cholesterol metabolite, 27-hydroxycholesterol induces hyperplasia in an androgen receptor-dependent manner in normal prostate RWPE-1 cells

Abstract

Abstract For every 6 men, 1 will be diagnosed with prostate cancer (PCa). Moreover, benign prostatic hyperplasia (BPH) also occurs in 50% of men over the age of 50. Although Androgens are known to play an important role in PCa and BPH, some evidence shows estrogens may be involved as well. Recently a cholesterol oxidized metabolite (oxysterol), 27- hydroxycholesterol (27-OHC) was found to bind to estrogen receptor(ER) and act as a selective ER modulator (SERM). 27-OHC is the most prevalent cholesterol metabolite present in the blood with levels increasing with oxidative stress and age, especially in men. The role of 27-OHC in PCa and BPH remains to be investigated. We propose that 27-OHC has deleterious effect in PCa and BPH, whereas the effect on BPH may be androgen dependent. We recently found that incubation with 27-OHC of RWPE-1 (normal epithelial) and LNCaP (cancer cells) increased cell proliferation in both cell lines. Interestingly, upon incubation of RWPE-1 and LNCaP with 27-OHC, we observed an increase in androgen receptor (AR) activity in RWPE-1, not in LNCaP. Furthermore, we found an increase in AR binding to the Androgen Response Element upon exposure of RWPE-1 to 27-OHC. We also found that upon silencing AR gene expression, 27-OHC-induced proliferation in RWPE-1 was markedly attenuated. Additionally, 27-OHC also diminished Docetaxel-mediated apoptosis in RWPE-1. Altogether, our results propose dysregulated levels of 27-OHC as a new risk factor for BPH and PCa. This indicates a novel role for 27-OHC in the etiopathogenesis of BPH and PCa. Citation Format: Shaneabbas Raza, Megan Meyer, Bin Guo, Kimberly Hammer, Othman Ghribi. The cholesterol metabolite, 27-hydroxycholesterol induces hyperplasia in an androgen receptor-dependent manner in normal prostate RWPE-1 cells. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B20.