| Telomere maintenance in telomerase-positive human ovarian SKOV-3 cells cannot be retarded by complete inhibition of telomerase. | |
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MedLine Citation:
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PMID: 12220625 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The two known mechanisms for telomere maintenance in eukaryocytes are telomerase in telomerase-positive cells and alternative lengthening of telomeres (ALT) in telomerase-negative cells. We report here that telomere maintenance in the telomerase-positive human ovarian SKOV-3 cells was not affected by inhibition of telomerase. For comparison, the effect of telomerase inhibitors on telomere maintenance in another telomerase-positive cell line (i.e. human pharynx FaDu cells) and the telomerase-negative human osteosarcoma Saos-2 cells was examined. Telomerase activity was measured using a modified telomeric repeat amplification protocol and telomere length was measured using a solution hybridization-based method and fluorescence in situ hybridization. A reverse transcriptase inhibitor (3'-azido-deoxythymidine or AZT) and an antisense against a component of human telomerase RNA (antisense hTR) were used to inhibit telomerase. FaDu and SKOV-3 cells showed comparable baseline telomerase activity. Telomerase activity in both cells was inhibited about equally by AZT (maximal inhibition of approximately 80%) and by expression of antisense hTR (complete inhibition in SKOV-3 cells and maximal inhibition of approximately 80% in FaDu cells). However, treatment with telomerase inhibitors resulted in approximately 50% telomere shortening in FaDu cells but had no effect on SKOV-3 nor Saos-2 cells. SKOV-3 cells did not show the characteristic features of ALT (i.e. heterogeneous telomere length and promyelocytic leukemia bodies), whereas these ALT features were observed in Saos-2 cells. Collectively, these results suggest the existence of a telomerase-independent mechanism of telomere maintenance in the telomerase-positive SKOV-3 cells. |
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Authors:
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Yuebo Gan; Yiqun Mo; Jeffrey Johnston; Jie Lu; M Guillaume Wientjes; Jessie L-S Au |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: FEBS letters Volume: 527 ISSN: 0014-5793 ISO Abbreviation: FEBS Lett. Publication Date: 2002 Sep |
Date Detail:
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Created Date: 2002-09-10 Completed Date: 2002-11-08 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0155157 Medline TA: FEBS Lett Country: Netherlands |
Other Details:
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Languages: eng Pagination: 10-4 Citation Subset: IM |
Affiliation:
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College of Pharmacy, The Ohio State University, 500 West 12th Avenue, Columbus, OH 43210, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Cells, Cultured Enzyme Inhibitors / pharmacology Female Humans Oligonucleotides, Antisense / pharmacology Osteosarcoma / metabolism, pathology Ovary / cytology*, drug effects, physiology* Pharynx / cytology, physiology Telomerase / antagonists & inhibitors*, genetics, metabolism Telomere / drug effects, physiology* Zidovudine / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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R01CA77091/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Oligonucleotides, Antisense; 30516-87-1/Zidovudine; EC 2.7.7.49/Telomerase |
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