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 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.
Vanden Abeele
Fabien
F
Laboratoire de Physiologie Cellulaire, INSERM EPI-9938, Universite des Sciences et Technologies de Lille, Batiment SN3, 59655 Villeneuve d'Ascq Cedex, France.
Skryma
Roman
R
Shuba
Yaroslav
Y
Van Coppenolle
Fabien
F
Slomianny
Christian
C
Roudbaraki
Morad
M
Mauroy
Brigitte
B
Wuytack
Frank
F
Prevarskaya
Natalia
N
D017209:Apoptosis; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D037282:Calreticulin; D004553:Electric Conductivity; D004594:Electrophysiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008297:Male; D018408:Patch-Clamp Techniques; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D014407:Tumor Cells, Cultured
D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D037282:Calreticulin; D019253:Proto-Oncogene Proteins c-bcl-2; D012261:Ribonucleoproteins; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium