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Store-operated Ca2+ channel control homeostasis between extracellular Ca2+ reservoir and intracellular Ca2+ storage in the signaling cascade of apoptosis in a wide variety of cells including the prostate epithelia. We have a unique tumorigenic prostatic epithelial cell line (NRP-154) that undergoes apoptosis in response to TGF-β treatment and sustained activation of store-operated Ca2+ entry (SOCE). NRP-154 has a luminal cell phenotype and lacks the expression of androgen receptor, and thus may represent a model for studying androgen-independent prostate cancer. We found that NRP-154 cells could sustain overexpression of exogenous Bax protein, which is opposite to that occurs in non-tumor cells where Bax functions as a ubiquitous stimulator of apoptosis. To elucidate the synergistic function between Ca and Bax in apoptosis of NRP-154 cells, we employed fluorescence measurement of Ca2+ transients and Mn2+-quenching of Fura-2 as indicator of SOC-mediated unidirectional ion influx. We found that NRP-154 cells stably overexpressing Bax displayed a significant decrese in IP3 receptor-mediated Ca2+ release from endoplasmic reticulum and remarkable down-regulation of SOCE. The reduction of SOCE showed high correlation with calpain-mediated cleavage of Bax at the amino-terminus, which is linked to the different degree of sensitivity to TGF-β induced apoptosis in NRP-154 cells. Our data indicate that overexpression of Bax resulted in compromised function of SOCE and this change might be a cellular protective mechanism that reduces the synergy between Ca2+ and Bax in the initiation of apoptosis in NRP-154 cells.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]