Document Detail


Resistance to senescence induction and telomere shortening by a G-quadruplex ligand inhibitor of telomerase.
MedLine Citation:
PMID:  14559794     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The molecular mechanisms induced by G-quadruplex ligands to trigger senescence in mammalian cells are still unknown, although the critical role of telomerase is highly suspected. JFA2 cells selected for resistance to senescence induced by the G-quadruplex ligand 12459 presented an overexpression of hTERT transcript that correlated to a functional increase in telomerase activity and telomere length. Consistently, treatment with 12459 failed to trigger senescence and telomere shortening in JFA2 cells. Resistant cells also presented cross-resistance for senescence induction to telomestatin, another G-quadruplex ligand from a different series, but not to other anticancer agents, indicating the selectivity of the resistance mechanism. We, thus, provide evidence that telomerase activity and telomere length are key cellular determinants of the resistance to G-quadruplex ligands.
Authors:
Dennis Gomez; Nassera Aouali; Alexandra Renaud; Céline Douarre; Kazuo Shin-Ya; Jamal Tazi; Sophie Martinez; Chantal Trentesaux; Hamid Morjani; Jean-François Riou
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer research     Volume:  63     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  2003 Oct 
Date Detail:
Created Date:  2003-10-15     Completed Date:  2003-12-03     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6149-53     Citation Subset:  IM    
Affiliation:
Onco-Pharmacologie, Unité Mixte de Recherche (UMR), 6142 Centre National de la Recherche Scientifique (CNRS), Unité de Formation et de Recherche de Pharmacie, Université de Reims Champagne-Ardenne, 51096 Reims Cedex, France.
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MeSH Terms
Descriptor/Qualifier:
Cell Aging / drug effects,  physiology
Cell Line, Tumor
DNA / metabolism
DNA-Binding Proteins
Drug Resistance, Neoplasm
Enzyme Inhibitors / pharmacology*
G-Quadruplexes
Humans
Ligands
Lung Neoplasms / drug therapy*,  enzymology,  pathology
RNA, Messenger / biosynthesis,  genetics
Telomerase / antagonists & inhibitors*,  biosynthesis,  genetics
Telomere / drug effects*,  physiology
Triazines / pharmacology*
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Enzyme Inhibitors; 0/Ligands; 0/RNA, Messenger; 0/Triazines; 9007-49-2/DNA; EC 2.7.7.49/Telomerase

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


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