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A gene expression signature classifying telomerase and ALT immortalisation reveals an hTERT regulatory network and suggests a mesenchymal stem cell origin for ALT
Telomere length is maintained by 2 known mechanisms, activation of telomerase or alternative lengthening of telomeres (ALT). The molecular mechanisms regulating the ALT phenotype are poorly understood and it is unknown how the decision of which pathway to activate is made at the cellular level. We h...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875172/ https://www.ncbi.nlm.nih.gov/pubmed/19684619 http://dx.doi.org/10.1038/onc.2009.238 |
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author | Lafferty-Whyte, Kyle Cairney, Claire J. Will, Malcolm B. Serakinci, Nedime Daidone, Maria-Grazia Zaffaroni, Nadia Bilsland, Alan Keith, W. Nicol |
author_facet | Lafferty-Whyte, Kyle Cairney, Claire J. Will, Malcolm B. Serakinci, Nedime Daidone, Maria-Grazia Zaffaroni, Nadia Bilsland, Alan Keith, W. Nicol |
author_sort | Lafferty-Whyte, Kyle |
collection | PubMed |
description | Telomere length is maintained by 2 known mechanisms, activation of telomerase or alternative lengthening of telomeres (ALT). The molecular mechanisms regulating the ALT phenotype are poorly understood and it is unknown how the decision of which pathway to activate is made at the cellular level. We have shown previously that active repression of telomerase gene expression by chromatin remodelling of the promoters is one mechanism of regulation, however other genes and signalling networks are likely to be required to regulate telomerase and maintain the ALT phenotype. Using gene expression profiling we have uncovered a signature of 1305 genes to distinguish telomerase positive and ALT cell lines. By combining this with gene expression profiles of liposarcoma tissue samples we refined this signature to 297 genes. Network analysis of known interactions between genes within this signature revealed a regulatory signalling network consistent with a model of hTERT repression in ALT cell lines and liposarcomas. This network expands on our existing knowledge of hTERT regulation and provides a platform to understand differential regulation of hTERT in different tumour types and normal tissues. We also show evidence to suggest a novel mesenchymal stem cell origin for ALT immortalisation in cell lines and mesenchymal tissues. |
format | Text |
id | pubmed-2875172 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
record_format | MEDLINE/PubMed |
spelling | pubmed-28751722010-05-24 A gene expression signature classifying telomerase and ALT immortalisation reveals an hTERT regulatory network and suggests a mesenchymal stem cell origin for ALT Lafferty-Whyte, Kyle Cairney, Claire J. Will, Malcolm B. Serakinci, Nedime Daidone, Maria-Grazia Zaffaroni, Nadia Bilsland, Alan Keith, W. Nicol Oncogene Article Telomere length is maintained by 2 known mechanisms, activation of telomerase or alternative lengthening of telomeres (ALT). The molecular mechanisms regulating the ALT phenotype are poorly understood and it is unknown how the decision of which pathway to activate is made at the cellular level. We have shown previously that active repression of telomerase gene expression by chromatin remodelling of the promoters is one mechanism of regulation, however other genes and signalling networks are likely to be required to regulate telomerase and maintain the ALT phenotype. Using gene expression profiling we have uncovered a signature of 1305 genes to distinguish telomerase positive and ALT cell lines. By combining this with gene expression profiles of liposarcoma tissue samples we refined this signature to 297 genes. Network analysis of known interactions between genes within this signature revealed a regulatory signalling network consistent with a model of hTERT repression in ALT cell lines and liposarcomas. This network expands on our existing knowledge of hTERT regulation and provides a platform to understand differential regulation of hTERT in different tumour types and normal tissues. We also show evidence to suggest a novel mesenchymal stem cell origin for ALT immortalisation in cell lines and mesenchymal tissues. 2009-08-17 2009-10-29 /pmc/articles/PMC2875172/ /pubmed/19684619 http://dx.doi.org/10.1038/onc.2009.238 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Lafferty-Whyte, Kyle Cairney, Claire J. Will, Malcolm B. Serakinci, Nedime Daidone, Maria-Grazia Zaffaroni, Nadia Bilsland, Alan Keith, W. Nicol A gene expression signature classifying telomerase and ALT immortalisation reveals an hTERT regulatory network and suggests a mesenchymal stem cell origin for ALT |
title | A gene expression signature classifying telomerase and ALT immortalisation reveals an hTERT regulatory network and suggests a mesenchymal stem cell origin for ALT |
title_full | A gene expression signature classifying telomerase and ALT immortalisation reveals an hTERT regulatory network and suggests a mesenchymal stem cell origin for ALT |
title_fullStr | A gene expression signature classifying telomerase and ALT immortalisation reveals an hTERT regulatory network and suggests a mesenchymal stem cell origin for ALT |
title_full_unstemmed | A gene expression signature classifying telomerase and ALT immortalisation reveals an hTERT regulatory network and suggests a mesenchymal stem cell origin for ALT |
title_short | A gene expression signature classifying telomerase and ALT immortalisation reveals an hTERT regulatory network and suggests a mesenchymal stem cell origin for ALT |
title_sort | gene expression signature classifying telomerase and alt immortalisation reveals an htert regulatory network and suggests a mesenchymal stem cell origin for alt |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875172/ https://www.ncbi.nlm.nih.gov/pubmed/19684619 http://dx.doi.org/10.1038/onc.2009.238 |
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