Long telomeres bypass the requirement for telomere maintenance in human tumorigenesis

Long telomeres bypass the requirement for telomere maintenance in human tumorigenesis

Despite the importance of telomere maintenance in cancer cell survival via the elongation of telomeres by telomerase reverse transcriptase (TERT) or Alternative Lengthening of Telomeres (ALT), it had not been tested directly whether telomere maintenance is dispensable for human tumorigenesis. We eng...

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Main Authors: Taboski, Michael A. S., Sealey, David C. F., Dorrens, Jennifer, Tayade, Chandrakant, Betts, Dean H., Harrington, Lea
Format: Online
Language:English
Published: 2012
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3406325/
id pubmed-3406325
recordtype oai_dc
spelling pubmed-34063252012-07-27 Long telomeres bypass the requirement for telomere maintenance in human tumorigenesis Taboski, Michael A. S. Sealey, David C. F. Dorrens, Jennifer Tayade, Chandrakant Betts, Dean H. Harrington, Lea Article Despite the importance of telomere maintenance in cancer cell survival via the elongation of telomeres by telomerase reverse transcriptase (TERT) or Alternative Lengthening of Telomeres (ALT), it had not been tested directly whether telomere maintenance is dispensable for human tumorigenesis. We engineered human tumor cells containing loxP-flanked hTERT to enable extensive telomere elongation prior to complete hTERT excision. Despite unabated telomere erosion, hTERT-excised cells formed tumors in mice and proliferated in vitro for up to one year. Telomerase reactivation or ALT was not observed, and the eventual loss of telomeric signal coincided with loss of tumorigenic potential and cell viability. Crisis was averted via the reintroduction of active but not inactive hTERT. Thus, telomere maintenance is dispensable for human tumorigenesis when telomere reserves are long. Yet, despite telomere instability and the presence of oncogenic RAS, human tumors remain susceptible to crisis induced by critically short telomeres. 2012-02-02 2012-02-23 /pmc/articles/PMC3406325/ /pubmed/22832159 http://dx.doi.org/10.1016/j.celrep.2011.12.004 Text en https://creativecommons.org/licenses/by-nc-nd/3.0/ Open Access under CC BY-NC-ND 3.0 (https://creativecommons.org/licenses/by-nc-nd/3.0/) license.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Taboski, Michael A. S.
Sealey, David C. F.
Dorrens, Jennifer
Tayade, Chandrakant
Betts, Dean H.
Harrington, Lea
spellingShingle Taboski, Michael A. S.
Sealey, David C. F.
Dorrens, Jennifer
Tayade, Chandrakant
Betts, Dean H.
Harrington, Lea
Long telomeres bypass the requirement for telomere maintenance in human tumorigenesis
author_facet Taboski, Michael A. S.
Sealey, David C. F.
Dorrens, Jennifer
Tayade, Chandrakant
Betts, Dean H.
Harrington, Lea
author_sort Taboski, Michael A. S.
title Long telomeres bypass the requirement for telomere maintenance in human tumorigenesis
title_short Long telomeres bypass the requirement for telomere maintenance in human tumorigenesis
title_full Long telomeres bypass the requirement for telomere maintenance in human tumorigenesis
title_fullStr Long telomeres bypass the requirement for telomere maintenance in human tumorigenesis
title_full_unstemmed Long telomeres bypass the requirement for telomere maintenance in human tumorigenesis
title_sort long telomeres bypass the requirement for telomere maintenance in human tumorigenesis
description Despite the importance of telomere maintenance in cancer cell survival via the elongation of telomeres by telomerase reverse transcriptase (TERT) or Alternative Lengthening of Telomeres (ALT), it had not been tested directly whether telomere maintenance is dispensable for human tumorigenesis. We engineered human tumor cells containing loxP-flanked hTERT to enable extensive telomere elongation prior to complete hTERT excision. Despite unabated telomere erosion, hTERT-excised cells formed tumors in mice and proliferated in vitro for up to one year. Telomerase reactivation or ALT was not observed, and the eventual loss of telomeric signal coincided with loss of tumorigenic potential and cell viability. Crisis was averted via the reintroduction of active but not inactive hTERT. Thus, telomere maintenance is dispensable for human tumorigenesis when telomere reserves are long. Yet, despite telomere instability and the presence of oncogenic RAS, human tumors remain susceptible to crisis induced by critically short telomeres.
publishDate 2012
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3406325/
_version_ 1611545917150724096

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