The proliferative effect of estradiol on human prostate stromal cells is mediated through activation of ERK

Background Estrogen is involved in the development and progression of benign prostatic hyperplasia (BPH). It can stimulate proliferation of prostate stromal cells (PrSCs). However, the exact mechanism remains unclear. Methods We used the primary cultured human PrSCs and a prostate stromal cell line, WPMY‐1, to examine the signaling pathways involved in estrogen‐mediated proliferation of PrSCs. Cells were treated with 17β‐estradiol (E2) or BSA‐E2. Cell proliferation was assessed by the MTT assay and by cell counting. Western blot analysis was used to determine the status of activation of ERK1/2. Results Results indicated that both E2 and BSA‐E2 stimulated proliferation of primary PrSCs and WPMY‐1 cells. ERK was rapidly activated by E2 and BSA‐E2. PD98059, which is a selective ERK inhibitor, significantly inhibited estrogen‐induced cell proliferation. PrSCs expressed estrogen receptor α (ERα) and GPR30 but not ERβ. Small hairpin RNA (shRNA) to ERα, but not to GPR30, blocked estrogen‐mediated ERK activation and cell proliferation. Conclusions The results indicated that estrogen could activate ERK pathway through the non‐genomic ERα pathway, leading to proliferation of PrSCs. Prostate 68: 508–516, 2008. © 2008 Wiley‐Liss, Inc.