Store-operated Ca2+ channels in prostate cancer epithelial cells: function, regulation, and role in carcinogenesis

• Published in: Cell calcium (Edinburgh) Vol. 33; no. 5-6; pp. 357 - 373
• Main Authors: Vanden Abeele, F, Shuba, Y, Roudbaraki, M, Lemonnier, L, Vanoverberghe, K, Mariot, P, Skryma, R, Prevarskaya, N
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier 01.05.2003
• Subjects: Biomarkers; Calcium - metabolism; Calcium Channels - genetics; Calcium Channels - metabolism; Cancer; Cellular Biology; Electrophysiology; Endoplasmic Reticulum - metabolism; Epithelial Cells - metabolism; Epithelial Cells - pathology; Human health and pathology; Humans; Kinetics; Life Sciences; Male; Oligonucleotides, Antisense - pharmacology; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; RNA, Messenger - drug effects; Subcellular Processes; TRPC Cation Channels; TRPV Cation Channels; Tumor Cells, Cultured; Urology and Nephrology
• ISSN: 0143-4160; 1532-1991
• DOI: 10.1016/s0143-4160(03)00049-6

Ca2+ homeostasis mechanisms, in which the Ca2+ entry pathways play a key role, are critically involved in both normal function and cancerous transformation of prostate epithelial cells. Here, using the lymph node carcinoma of the prostate (LNCaP) cell line as a major experimental model, we characterize prostate-specific store-operated Ca2+ channels (SOCs)--a primary Ca2+ entry pathway for non-excitable cells--for the first time. We show that prostate-specific SOCs share major store-dependent, kinetic, permeation, inwardly rectifying, and pharmacological (including dual, potentiation/inhibition concentration-dependent sensitivity to 2-APB) properties with "classical" Ca2+ release-activated Ca2+ channels (CRAC), but have a higher single channel conductance (3.2 and 12pS in Ca2+- and Na+-permeable modes, respectively). They are subject to feedback inhibition via Ca2+-dependent PKC, CaMK-II and CaM regulatory pathways and are functionally dependent on caveolae integrity. Caveolae also provide a scaffold for spatial co-localization of SOCs with volume-regulated anion channels (VRAC) and their Ca2+-mediated interaction. The TRPC1 and TRPV6 members of the transient receptor potential (TRP) channel family are the most likely molecular candidates for the formation of prostate-specific endogenous SOCs. Differentiation of LNCaP cells to an androgen-insensitive, apoptotic-resistant neuroendocrine phenotype downregulates SOC current. We conclude that prostate-specific SOCs are important determinants in the transition to androgen-independent prostate cancer.