Effect of TERT and ATM on gene expression profiles in human fibroblasts
Autor: | Scott Zuyderduyn, Steven J.M. Jones, Agnes Baross, Mike Schertzer, Peter M. Lansdorp, Marco A. Marra |
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Rok vydání: | 2004 |
Předmět: |
Genome instability
Male Cancer Research Telomerase Cell Cycle Proteins Ataxia Telangiectasia Mutated Proteins Biology Protein Serine-Threonine Kinases Ataxia Telangiectasia Transduction Genetic Gene expression Genetics Humans Telomerase reverse transcriptase Serial analysis of gene expression Child Gene Cells Cultured Gene Library Skin Expressed Sequence Tags Gene Expression Profiling Tumor Suppressor Proteins Infant Newborn Fibroblasts Telomere Molecular biology Gene expression profiling DNA-Binding Proteins Retroviridae Gene Expression Regulation Genes |
Zdroj: | Genes, chromosomescancer. 39(4) |
ISSN: | 1045-2257 |
Popis: | Telomeres protect chromosomes from degradation, end-to-end fusion, and illegitimate recombination. Loss of telomeres may lead to cell death or senescence or may cause genomic instability, leading to tumor formation. Expression of human telomerase reverse transcriptase (TERT) in human fibroblast cells elongates their telomeres and extends their lifespan. Ataxia telangiectasia mutated (ATM) deficiency in A-T human fibroblasts results in accelerated telomere shortening, abnormal cell-cycle response to DNA damage, and early senescence. Gene expression profiling was performed by serial analysis of gene expression (SAGE) on BJ normal human skin fibroblasts, A-T cells, and BJ and A-T cells transduced with TERT cDNA and expressing telomerase activity. In the four SAGE libraries, 36,921 unique SAGE tags were detected. Pairwise comparisons between the libraries showed differential expression levels of 1%-8% of the tags. Transcripts affected by both TERT and ATM were identified according to expression patterns, making them good candidates for further studies of pathways affected by both TERT and ATM. These include MT2A, P4HB, LGALS1, CFL1, LDHA, S100A10, EIF3S8, RANBP9, and SEC63. These genes are involved in apoptosis or processes related to cell growth, and most have been found to be deregulated in cancer. Our results have provided further insight into the roles of TERT and ATM by identifying genes likely to be involved in their function. Supplementary material for this article can be found on the Genes, Chromosomes and Cancer website at http://www.interscience.wiley.com/jpages/1045-2257/suppmat/index.html. |
Databáze: | OpenAIRE |
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