Reference : Disruption of the interaction between PMCA2 and calcineurin triggers apoptosis and en...
Scientific journals : Article
Human health sciences : Oncology
http://hdl.handle.net/10993/18353
Disruption of the interaction between PMCA2 and calcineurin triggers apoptosis and enhances paclitaxel-induced cytotoxicity in breast cancer cells.
English
Baggott, Rhiannon R. [> >]
Mohamed, Tamer M. A. [> >]
Oceandy, Delvac [> >]
Holton, Marylouisa [> >]
Blanc, Marie Cecile [> >]
Roux-Soro, Sandrine C. [> >]
Brown, Sarah [> >]
Brown, James E. [> >]
Cartwright, Elizabeth J. [> >]
Wang, Weiguang [> >]
Neyses, Ludwig mailto [University of Luxembourg > Research Office]
Armesilla, Angel L. [> >]
2012
Carcinogenesis
33
12
2362-8
Yes (verified by ORBilu)
International
0143-3334
1460-2180
England
[en] Antineoplastic Agents, Phytogenic/pharmacology ; Apoptosis/drug effects ; Breast Neoplasms/drug therapy/pathology ; Calcineurin/physiology ; Cell Line, Tumor ; Fas Ligand Protein/analysis ; Genes, p53 ; Humans ; NFATC Transcription Factors/physiology ; Paclitaxel/pharmacology ; Plasma Membrane Calcium-Transporting ATPases/physiology ; Protein Binding/drug effects ; Signal Transduction
[en] Cancer is caused by defects in the signalling mechanisms that govern cell proliferation and apoptosis. It is well known that calcium-dependent signalling pathways play a critical role in cell regulation. A tight control of calcium homeostasis by transporters and channel proteins is required to assure a proper functioning of the calcium-sensitive signal transduction pathways that regulate cell growth and apoptosis. The plasma membrane calcium ATPase 2 (PMCA2) has been recently identified as a negative regulator of apoptosis that can play a significant role in cancer progression by conferring cells resistance to apoptosis. We have previously reported an inhibitory interaction between PMCA2 and the calcium-activated signalling molecule calcineurin in breast cancer cells. Here, we demonstrate that disruption of the PMCA2/calcineurin interaction in a variety of human breast cancer cells results in activation of the calcineurin/NFAT pathway, upregulation in the expression of the pro-apoptotic protein Fas Ligand and in a concomitant loss of cell viability. Reduction in cell viability is the consequence of an increase in cell apoptosis. Impairment of the PMCA2/calcineurin interaction enhances paclitaxel-mediated cytotoxicity of breast tumoral cells. Our results suggest that therapeutic modulation of the PMCA2/calcineurin interaction might have important clinical applications to improve current treatments for breast cancer patients.
http://hdl.handle.net/10993/18353
10.1093/carcin/bgs282
http://carcin.oxfordjournals.org/content/33/12/2362.long

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