| Antisense oligonucleotide-mediated inhibition of hTERT, but not hTERC, induces rapid cell growth decline and apoptosis in the absence of telomere shortening in human prostate cancer cells. | |
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MedLine Citation:
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PMID: 15737568 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Recent evidence points to a novel function of human telomerase reverse transcriptase (hTERT) in promoting tumour cell survival, which might be independent of the telomere-elongating activity of the enzyme. To test this hypothesis, we evaluated comparatively the effects of telomerase inhibition, accomplished through antisense oligonucleotide-mediated interference with hTERT or human telomerase RNA component (hTERC), on the proliferative potential of DU145 human prostate cancer cells. Exposure of cells to a 2'-O-methyl-RNA phosphorothioate oligonucleotide targeting a splicing site within hTERT pre-mRNA induced almost complete inhibition of telomerase activity as a consequence of a marked reduction of the hTERT mRNA expression level, an early decline of DU145 cell growth and apoptotic cell death without any appreciable telomere shortening. Conversely, exposure of DU145 cells to a 2'-O-methyl-RNA phosphorothioate oligonucleotide targeting the template region of hTERC failed to interfere with cell proliferation in spite of the almost complete abrogation of telomerase activity. These results extend and corroborate earlier evidence in favour of an enzymatic activity-independent mechanism by which hTERT maintains tumour cell survival and proliferation. |
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Authors:
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Marco Folini; Cinzia Brambilla; Raffaella Villa; Paolo Gandellini; Sara Vignati; Francesco Paduano; Maria Grazia Daidone; Nadia Zaffaroni |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2005-01-20 |
Journal Detail:
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Title: European journal of cancer (Oxford, England : 1990) Volume: 41 ISSN: 0959-8049 ISO Abbreviation: Eur. J. Cancer Publication Date: 2005 Mar |
Date Detail:
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Created Date: 2005-03-01 Completed Date: 2005-05-03 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9005373 Medline TA: Eur J Cancer Country: England |
Other Details:
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Languages: eng Pagination: 624-34 Citation Subset: IM |
Affiliation:
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Dipartimento di Oncologia Sperimentale, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milan, Italy. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis Cell Division Cell Line, Tumor DNA-Binding Proteins Humans Male Oligonucleotides, Antisense / pharmacology* Prostatic Neoplasms / genetics*, pathology Telomerase / antagonists & inhibitors*, metabolism Telomere / pathology* |
| Chemical | |
Reg. No./Substance:
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0/DNA-Binding Proteins; 0/Oligonucleotides, Antisense; EC 2.7.7.49/Telomerase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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