Both nongenomic and genomic effects are involved in estradiol's enhancing the phenotype of smooth muscle cells in cultured prostate stromal cells

Zhisong Zhang, Liang Wang, Mei Mei, Yan Zhu, Xiaoling Du, Chung Lee, Irwin Park, Ju Zhang*, Jiandang Shi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

BACKGROUND. Stromal smooth muscle cells (SMCs) play an important role in the pathogenesis and clinical symptom of benign prostatic hyperplasia. We had reported that estrogen enhances the phenotype of SMC in cultured prostate stromal cells (PRSCs). Here we further investigate the mechanism by which estrogen affects the differentiation of PRSCs. METHODS. Primary cultured PRSCs were stimulated with E2 or BSA-E2. The mRNA level of SMC-specific genes, smoothelin, andSM-MHCwere measured by qRT-PCR. The SM-HCprotein was measured by Western blot. The mRNA and protein levels of TGF-β1 were measured by qRTPCR and ELISA. The MAPK inhibitor PD98059, the estrogen receptor antagonist ICI182,780 and neutralizing antibody to TGF-β1 were used to reveal the mechanism of estrogen effect. RESULTS. E2 and BSA-E2 significantly up-regulate the expression of SMC-specific genes in PRSCs. Both forms of estrogen could increase the expression of TGF-β1, which can be blocked by pre-treating with PD98059. Moreover, PD98059 and TGF-β1 neutralizing antibody could abrogate the effect of BSA-E2 on cell differentiation. However, they could only inhibit part of E2-induced SMC phenotype enhancement. ICI182,780 could partially suppress the prodifferentiation effect of E2 but had no influence on the effect of BSA-E2. Combined treatment with ICI182,780 and PD98059 can completely abrogate the effect of E2. CONCLUSIONS. Estrogen could promote the expression of TGF-β1 in PRSCs through nongenomic activation ofMAPKpathway, and in turn enhance theSMCphenotype. Besides for this nongenomic effect, estrogen can also enhance the SMC phenotype through classical genomic action.

Original languageEnglish (US)
Pages (from-to)317-332
Number of pages16
JournalProstate
Volume70
Issue number3
DOIs
StatePublished - Feb 15 2010

Keywords

  • Estrogen
  • Genomic effect
  • Nongenomic effect
  • SMC

ASJC Scopus subject areas

  • Oncology
  • Urology

Fingerprint Dive into the research topics of 'Both nongenomic and genomic effects are involved in estradiol's enhancing the phenotype of smooth muscle cells in cultured prostate stromal cells'. Together they form a unique fingerprint.

Cite this