Store-operated Ca2+ current in prostate cancer epithelial cells -: Role of endogenous Ca2+ transporter type 1

Ca2+ influx via store-operated channels (SOCs) following stimulation of the plasma membrane receptors is the key event controlling numerous processes in nonexcitable cells. The human transient receptor potential vanilloid type 6 channel, originally termed Ca2+ transporter type 1 (CaT1) protein, is one of the promising candidates for the role of endogenous SOC, although investigations of its functions have generated considerable controversy. In order to assess the role of CaT1 in generating endogenous store-operated Ca2+ current (Is,c) in the lymph node carcinoma of the prostate (LN-CaP) human prostate cancer epithelial cell line, we manipulated its endogenous levels by means of antisense hybrid depletion or pharmacological up-regulation (antiandrogen treatment) combined with functional evaluation of Isoc. Antisense hybrid depletion of CaT1 decreased Isoc in LNCaP cells by similar to50%, whereas enhancement of CaT1 levels by 60% in response to Casodex treatment potentiated Isoc by 30%. The functional characteristics of Isoc in LNCaP cells were similar in many respects to those reported for heterologously expressed CaT1, although 2-aminoethoxydiphenyl borate sensitivity and lack of constitutive current highlighted notable departures. Our results suggest that CaT1 is definitely involved in Isoc, but it may constitute only a part of the endogenous SOC, which in general may be a heteromultimeric channel composed of homologous CaT1 and other transient receptor potential subunits.