Bcl-2-dependent modulation of Ca(2+) homeostasis and store-operated channels in prostate cancer cells

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 sto...

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Bibliographic Details
Published in:Cancer cell 2002-03, Vol.1 (2), p.169-179
Main Authors: Vanden Abeele, Fabien, Skryma, Roman, Shuba, Yaroslav, Van Coppenolle, Fabien, Slomianny, Christian, Roudbaraki, Morad, Mauroy, Brigitte, Wuytack, Frank, Prevarskaya, Natalia
Format: Article
Language:English
Subjects:
Apoptosis
Blotting, Western
Calcium - metabolism
Calcium Channels - metabolism
Calcium-Binding Proteins - metabolism
Calcium-Transporting ATPases - metabolism
Calreticulin
Electric Conductivity
Electrophysiology
Endoplasmic Reticulum - metabolism
Homeostasis
Humans
Male
Patch-Clamp Techniques
Prostatic Neoplasms - genetics
Prostatic Neoplasms - metabolism
Proto-Oncogene Proteins c-bcl-2 - genetics
Proto-Oncogene Proteins c-bcl-2 - metabolism
Ribonucleoproteins - metabolism
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Tumor Cells, Cultured
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Summary: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.
ISSN:1535-6108
DOI:10.1016/S1535-6108(02)00034-X