Document Detail


Cancer cell cycle modulated by a functional coupling between sigma-1 receptors and Cl- channels.
MedLine Citation:
PMID:  17121836     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The sigma-1 receptor is an intracellular protein characterized as a tumor biomarker whose function remains mysterious. We demonstrate herein for the first time that highly selective sigma ligands inhibit volume-regulated chloride channels (VRCC) in small cell lung cancer and T-leukemia cells. Sigma ligands and VRCC blockers provoked a cell cycle arrest underlined by p27 accumulation. In stably sigma-1 receptor-transfected HEK cells, the proliferation rate was significantly lowered by sigma ligands when compared with control cells. Sigma ligands produced a strong inhibition of VRCC in HEK-transfected cells but not in control HEK. Surprisingly, the activation rate of VRCC was dramatically delayed in HEK-transfected cells in the absence of ligands, indicating that sigma-1 receptors per se modulate cell regulating volume processes in physiological conditions. Volume measurements in hypotonic conditions revealed indeed that the regulatory volume decrease was delayed in HEK-transfected cells and virtually abolished in the presence of igmesine in both HEK-transfected and T-leukemic cells. Moreover, HEK-transfected cells showed a significant resistance to staurosporine-induced apoptosis volume decrease, indicating that sigma-1 receptors protect cancer cells from apoptosis. Altogether, our results show for the first time that sigma-1 receptors modulate "cell destiny" through VRCC and cell volume regulation.
Authors:
Adrien Renaudo; Sébastien L'Hoste; Hélène Guizouarn; Franck Borgèse; Olivier Soriani
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-11-22
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  282     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2007-01-22     Completed Date:  2007-04-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2259-67     Citation Subset:  IM    
Affiliation:
UNSA CNRS UMR 6548, Laboratoire de Physiologie Cellulaire & Moléculaire des Systèmes Intégrés, Université de Nice Sophia-Antipolis, 06108 Nice Cedex 2, France.
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MeSH Terms
Descriptor/Qualifier:
Cell Count
Cell Cycle* / physiology
Cell Line, Tumor
Cell Size*
Chloride Channels / metabolism*
Electrophysiology
Humans
Neoplasms / metabolism,  pathology
Receptors, sigma / metabolism*
Chemical
Reg. No./Substance:
0/Chloride Channels; 0/Receptors, sigma; 0/sigma-1 receptor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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