| Growth defects in mouse telomerase RNA-deficient cells expressing a template-mutated mouse telomerase RNA. | |
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MedLine Citation:
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PMID: 19056167 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cellular viability requires telomere maintenance, which, in mammals, is mainly mediated by the reverse transcriptase telomerase. Telomerase core components are a catalytic subunit TERT and an RNA subunit TR (hTR in humans, mTR in mouse) that carries the template to generate telomeres de novo. Telomere dysfunction can lead to senescence or apoptosis and impairs the continued growth of immortal cancerous cell lines. The introduction of a template-mutated hTR in telomerase-positive and telomerase-negative human cell lines results in dramatic growth defects. No study has addressed the consequences of expressing a template-mutated mTR in mouse immortal cell lines. Therefore, we analyzed the effects of long-term expression of a template-mutated mTR in the telomerase-positive and telomerase-negative murine cell lines CB17 and DKO301, respectively. Whereas the CB17 clones expressing the template-mutated mTR did not demonstrate any growth impairment, many of the DKO301 clones expressing the template-mutated mTR underwent growth and cell cycle defects and eventual cell death. These results suggest that in the absence of wild-type telomerase, the expression of the template-mutated mTR likely perturbs telomere function, leading to decreased cellular viability. Furthermore, whereas the expression of template-mutated hTR in telomerase-negative human cell lines leads to immediate cellular toxicity, the expression of the template-mutated mTR in the telomerase-negative mouse cell line did not. |
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Authors:
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Delphine T Marie-Egyptienne; Marie Eve Brault; Graeme A M Nimmo; J Arturo Londoño-Vallejo; Chantal Autexier |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-12-03 |
Journal Detail:
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Title: Cancer letters Volume: 275 ISSN: 1872-7980 ISO Abbreviation: Cancer Lett. Publication Date: 2009 Mar |
Date Detail:
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Created Date: 2009-02-10 Completed Date: 2009-02-24 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7600053 Medline TA: Cancer Lett Country: Ireland |
Other Details:
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Languages: eng Pagination: 266-76 Citation Subset: IM |
Affiliation:
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Department of Anatomy and Cell Biology, McGill University, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis Base Sequence Cell Division Cell Line, Transformed DNA Primers In Situ Hybridization, Fluorescence Mice Mutation* RNA / genetics* Reverse Transcriptase Polymerase Chain Reaction Telomerase / genetics* |
| Chemical | |
Reg. No./Substance:
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0/DNA Primers; 63231-63-0/RNA; EC 2.7.7.49/Telomerase; EC 2.7.7.49/Tert protein, mouse |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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