Effect of TERT and ATM on gene expression profiles in human fibroblasts.
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.
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
Agnes
A
Baross
Mike
M
Schertzer
Scott D
SD
Zuyderduyn
Steven J M
SJ
Jones
Marco A
MA
Marra
Peter M
PM
Lansdorp
D001260:Ataxia Telangiectasia / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D002648:Child; D004268:DNA-Binding Proteins; D020224:Expressed Sequence Tags; D005347:Fibroblasts / Q000737:chemistry* / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000235:genetics* / Q000502:physiology; D015723:Gene Library; D005796:Genes / Q000235:genetics / Q000502:physiology; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012190:Retroviridae / Q000235:genetics; D012867:Skin / Q000166:cytology / Q000473:pathology; D019098:Telomerase / Q000235:genetics*; D016615:Telomere / Q000201:enzymology / Q000235:genetics; D014161:Transduction, Genetic / Q000379:methods; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; C509186:TERT protein, human; D019098:Telomerase