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 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.
Zhang
Zhisong
Z
Department of Biochemistry and Molecular Biology, College of Life Sciences, Nankai University, Tianjin, China.
Duan
Lei
L
Du
Xiaoling
X
Ma
Hongshun
H
Park
Irwin
I
Lee
Chung
C
Zhang
Ju
J
Shi
Jiandang
J
D049109:Cell Proliferation; D002478:Cells, Cultured; D004958:Estradiol / Q000502:physiology*; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors; D004967:Estrogens / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D019886:Gastrin-Releasing Peptide / Q000037:antagonists & inhibitors; D006801:Humans; D008297:Male; D011467:Prostate / Q000166:cytology* / Q000378:metabolism*; D012313:RNA / Q000494:pharmacology; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism
D047628:Estrogen Receptor alpha; D004967:Estrogens; D005419:Flavonoids; C109584:GPER1 protein, human; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D004958:Estradiol; D012313:RNA; D019886:Gastrin-Releasing Peptide; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one