Expression of Proteinase-Activated Receptor-2 (PAR2) Is Androgen-Dependent in Stromal Cell Line (hPCPs) From Benign Prostatic Hyperplasia

BACKGROUND. Growth properties of the prostate are regulated by a variety of hormones and growth factors. Benign prostatic hyperplasia (BPH) is characterized by abnormal epithelial and stromal proliferation. Varying androgen hormone levels in elderly men are correlated with abnormal proliferations of the prostate. Proteinase-activated receptor-2 (PAR2), a subtype of G-protein-coupled receptors, is known to induce multiple biological processes. It could also play a key role in the proliferation and metastasis of prostate cancer, but its effect on BPH pathogenesis is to a great extent unknown. METHODS. Localization of PAR2 was determined both in pathologically altered and in normal prostate tissues by using immunohistochemical techniques. PAR2 activity was assessed by measuring changes in intracellular calcium [Ca2+](i) following stimulation of cultured stromal cells with a PAR2 agonist (trypsin) and a synthetic PAR2-activating peptide (AP). DHT-dependence of PAR2 expression in prostate cancer and prostatic stromal cell lines was examined with semi-quantitative and quantitative PCR. Cultured stromal cells (hPCPs) were stimulated with PAR2 AP and cell proliferation was determined through [H-3]-thymidine incorporation. RESULTS. In comparison to normal prostate, PAR2 expression was increased in BPH stroma. DHT induced a higher expression of PAR2 when sub-physiological DHT-levels were used. Higher levels of DHT produced reduced PAR2 expression. A mitogenic effect was induced by applying PAR2 AP to hPCPs-cells. CONCLUSIONS. In conclusion, we found that PAR2 expression is hormone-dependent in prostatic stromal cells with a negative correlation and we consider it to be an important factor in mitogenesis in BPH. Prostate 70: 1350-1358, 2010. (C) 2010 Wiley-Liss, Inc.