title: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Zhisong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Duan
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Du
authors.forename: Hongshun
authors.initials: H
authors.lastname: Ma
authors.forename: Irwin
authors.initials: I
authors.lastname: Park
authors.forename: Chung
authors.initials: C
authors.lastname: Lee
authors.forename: Ju
authors.initials: J
authors.lastname: Zhang
authors.forename: Jiandang
authors.initials: J
authors.lastname: Shi
mesh_terms: 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
chemical_list: 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