title: Differential effects of estrogen receptor ligands on regulation of dihydrotestosterone-induced             cell proliferation in endothelial and prostate cancer cells.
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.
authors.affiliation: The Third Xiangya Hospital, Central South University, Changsha, People's Republic of China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Weng
authors.forename: Jingjing
authors.initials: J
authors.lastname: Cai
authors.forename: Juan
authors.initials: J
authors.lastname: Wen
authors.forename: Hong
authors.initials: H
authors.lastname: Yuan
authors.forename: Kan
authors.initials: K
authors.lastname: Yang
authors.forename: Julianne
authors.initials: J
authors.lastname: Imperato-McGinley
authors.forename: Yuan-Shan
authors.initials: YS
authors.lastname: Zhu
mesh_terms: D000728:Androgens / Q000494:pharmacology; D001011:Aorta / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D019925:Cyclin A; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens; D006801:Humans; D008297:Male; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000728:Androgens; D019925:Cyclin A; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D013196:Dihydrotestosterone; D017430:Prostate-Specific Antigen