Author:

Keywords:

Apoptosis, Blotting, Western, Ca(2+)-Transporting ATPase, Calcium, Calcium Channels, Calcium-Binding Proteins, Calreticulin, Electric Conductivity, Electrophysiology, Endoplasmic Reticulum, Homeostasis, Humans, Male, Patch-Clamp Techniques, Prostatic Neoplasms, Proto-Oncogene Proteins c-bcl-2, Research Support, Non-U.S. Gov't, Ribonucleoproteins, Tumor Cells, Cultured, Science & Technology, Life Sciences & Biomedicine, Oncology, Cell Biology, CAPACITATIVE CALCIUM-ENTRY, ENDOPLASMIC-RETICULUM, APOPTOSIS, DEPLETION, CALRETICULIN, ACTIVATION, RECEPTOR, PROTEIN, DEATH, OVEREXPRESSION, Calcium-Transporting ATPases, Sarcoplasmic Reticulum Calcium-Transporting ATPases, 1109 Neurosciences, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, 3101 Biochemistry and cell biology, 3211 Oncology and carcinogenesis

Abstract:

Antiapoptotic oncoprotein Bcl-2 has extramitochondrial actions due to its localization on the endoplasmic reticulum (ER); however, the specific mechanisms of such actions remain unclear. Here we show that Bcl-2 overexpression in LNCaP prostate cancer epithelial cells results in downregulation of store-operated Ca(2+) current by decreasing the number of functional channels and inhibiting ER Ca(2+) uptake through a reduction in the expression of calreticulin and SERCA2b, two key proteins controlling ER Ca(2+) content. Furthermore, we demonstrate that Ca(2+) store depletion by itself is not sufficient to induce apoptosis in Bcl-2 overexpressing cells, and that sustained Ca(2+) entry via activated store-operated channels (SOCs) is required as well. Our data therefore suggest the pivotal role of SOCs in apoptosis and cancer progression.