title: Androgens induce increases in intracellular calcium via a G protein-coupled receptor in LNCaP prostate cancer cells.
abstract: The receptor mechanism of testosterone-induced nongenomic Ca2+ signaling in prostate cancer cells is poorly understood. In this study we investigated androgen-induced intracellular Ca2+ increases in LNCaP human prostate cancer cells with Fura-2 as a Ca2+ probe. 5alpha-dihydrotestosterone (DHT) produced fast and transient increases in intracellular Ca2+ in LNCaP cells in a concentration-dependent manner. These effects were abolished by extracellular Ca2+ removal or pretreatment with L-type Ca2+ channel inhibitors (nifedipine, verapamil, and diltiazem). Pretreatment with endoplasmic reticulum ryanodine receptor blocker (procaine) or phospholipase C inhibitor (neomycin sulfate) did not alter DHT-induced Ca2+ influx. The concentration of Ca2+ was also increased by impermeable testosterone conjugated to bovine serum albumin. Neither an antagonist of intracellular androgen receptors (cyproterone acetate) nor a protein synthesis inhibitor (cycloheximide) affected this fast Ca2+ influx. Furthermore, the effect of DHT was abolished in cells incubated with a G protein inhibitor (pertussis toxin) and a nonhydrolyzable analog of guanosine triphosphate (guanosine 5-[beta-thio]disphosphate) but not in cells incubated with the tyrosine kinase inhibitor genistein. These results indicate that androgens induced an L-type calcium channel-dependent intracellular Ca2+ increase in LNCaP prostate cancer cells. The rapid responses triggered by DHT did not appear to be mediated through classic intracellular androgen receptors, c-Src kinase-androgen receptor complex, or sex hormone-binding globulin but through a G protein-coupled receptor in LNCaP prostate cancer cells. These results may provide a new explanation for progression of prostate cancer.
authors.affiliation: Department of Urology, Changhai Hospital, 174 Changhai Road, Shanghai 200433, China.
authors.forename: Ying-Hao
authors.initials: YH
authors.lastname: Sun
authors.forename: Xu
authors.initials: X
authors.lastname: Gao
authors.forename: Yuan-Jie
authors.initials: YJ
authors.lastname: Tang
authors.forename: Chuan-Liang
authors.initials: CL
authors.lastname: Xu
authors.forename: Lin-Hui
authors.initials: LH
authors.lastname: Wang
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects; D020013:Calcium Signaling / Q000187:drug effects*; D045744:Cell Line, Tumor; D017373:Cyproterone Acetate / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004533:Egtazic Acid / Q000494:pharmacology; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000503:physiopathology*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*
chemical_list: D000728:Androgens; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D043562:Receptors, G-Protein-Coupled; D013196:Dihydrotestosterone; D017373:Cyproterone Acetate; D004533:Egtazic Acid; D002118:Calcium