Mechanism of estrogens-induced increases in intracellular Ca2+ in PC3 human prostate cancer cells

BACKGROUND. The effect of estrogens (diethylstilbestrol [DES], 17 beta -est radiol) on intracellular Ca2+ concentrations ([Ca2+](i)) in hormone-insensi tive PC3 human prostate cancer cells was examined. METHODS. [Ca2+](i) changes in suspended cells were measured by using the Ca 2+-sensitive fluorescent dye fura-2. RESULTS. Estrogens (1-20 muM) increased [Ca2+](i) concentration-dependently with DES being more potent. Ca2+ removal inhibited 50+/-10% of the signal. In Ca(2+-)free medium, pretreatment with 20 muM estrogens abolished the [C a2+](i) increases induced by 2 muM carbonylcyanide m-cholorophenylhydrazone (CCCP, a mitochondrial uncoupler) and 1 muM thapsigargin (an endoplasmic r eticulum Ca2+ pum inhibitor), but pretreatment with CCCP and thapsigargin d id not alter DES-induced Ca2+ increased [Ca2+](i) in cells pretreated with 1-20 muM estrogens in Ca(2+-)free medium. Pretreatment with 1 muM U73122 to block phospholipase C-coupled inositol 1,4,5-triphosphate formation did no t alter estrogens-induced Ca2+ release. The effect of 20 muM estrogen on [C a2+](i) was not affected by pretreatment with 0.1 muM estrogens. CONCLUSIONS. Estrogen induced significant Ca2+ release and Ca2+ influx in a n inositol 1,4,5-triphosphate-independent manner in PC3 cells. These effect s of estrogens on Ca2+ signaling appear to be nongenomic. Prostate 47:141-1 48, 2001. (C) 2001 Wiley-Liss, Inc.