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

Abstract

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 17beta-estradiol (E(2)) or BSA-E(2). 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 E(2) and BSA-E(2) stimulated proliferation of primary PrSCs and WPMY-1 cells. ERK was rapidly activated by E(2) and BSA-E(2). PD98059, which is a selective ERK inhibitor, significantly inhibited estrogen-induced cell proliferation. PrSCs expressed estrogen receptor alpha (ERalpha) and GPR30 but not ERbeta. Small hairpin RNA (shRNA) to ERalpha, 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 ERalpha pathway, leading to proliferation of PrSCs.