Differential effects of estrogen receptor ligands on regulation of dihydrotestosterone-induced cell proliferation in endothelial and prostate cancer cells

Weng,Chunyan; Cai,Jingjing; Wen,Juan; Yuan,Hong; Yang,Kan; Imperato-McGinley,Julianne; Zhu,Yuan-Shan

doi:10.3892/ijo.2012.1689

Differential effects of estrogen receptor ligands on regulation of dihydrotestosterone-induced cell proliferation in endothelial and prostate cancer cells

Authors:
- Chunyan Weng
- Jingjing Cai
- Juan Wen
- Hong Yuan
- Kan Yang
- Julianne Imperato-McGinley
- Yuan-Shan Zhu
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Affiliations: The Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, P.R. China, Department of Medicine/Endocrinology, Weill Cornell Medical College, New York, NY 10065, USA, Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, P.R. China
Published online on: November 6, 2012 https://doi.org/10.3892/ijo.2012.1689
Pages: 327-337

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Abstract

Androgen deprivation therapy of prostate cancer with estrogens shows significant cardiovascular side‑effects. To develop effective prostate cancer therapeutic agent(s) with minimal cardiovascular side‑effects, we compared the effects of various estrogen receptor (ER) ligands on the modulation of dihydrotestosterone (DHT) actions in LAPC-4 and LNCaP prostate cancer cells and human aortic endothelial cells (HAECs). DHT stimulated the proliferation of HAEC, LAPC-4 and LNCaP cells and induced PSA mRNA expression in LAPC-4 cells. These DHT actions were differentially modulated by ER ligands in a cell-dependent manner. In LAPC-4 cells, knockdown of ERβ expression partially eliminated the βE2 inhibition of DHT-induced LAPC-4 cell proliferation, and a parallel change was observed between ER ligand modulation of DHT-induced cell proliferation and cyclin A expression. The obtained data suggest that it is feasible to develop effective agent(s) for prostate cancer therapy with minimal cardiovascular side‑effects and 17α-estradiol and genistein are such potential agents.

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