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Series GSE2684 Query DataSets for GSE2684
Status Public on May 31, 2005
Title mTert overexpression in MEFs
Organism Mus musculus
Experiment type Expression profiling by array
Summary Recent studies suggest that telomerase promotes cell growth by mechanisms that extend beyond the rescue of critically short telomeres. The in vitro model of mTert overexpressing MEFs recapitulates fundamental aspects of the growth-promoting effects of mTert in vivo. First, in Terc-proficient cells, mTert overexpression favors escape from replicative senescence and enhances anchorage-independent growth in response to oncogenic stress, which fits well with previous data showing that mTert overexpression promotes tumor formation. Second, in Terc-deficient cells, retroviral transduction with mTert results in a delayed onset of immortalization and impairs colony formation in response to oncogenic stress, which is in agreement with the inhibitory effect of mTert overexpression on tumorigenesis in a Terc null mouse background. To unravel the molecular targets of telomerase that impact on cell growth, we compared the transcriptome of MEFs, before and after mTert introduction. We found that ectopic expression of mTert was associated with detectable gene expression changes (greater than 1.5-fold; validated by qRT-PCR) of 26 transcripts. Analysis of the observed transcriptional changes indicates that ectopic expression of mTert suppresses in a coordinated manner functionally related genes with overlapping roles in growth arrest, resistance to transformation, and apoptosis. We show that the majority of the telomerase target genes are growth-inhibitory, transforming growth factor-beta (TGF-beta) -inducible genes and provide functional evidence for the potential of telomerase to abrogate TGF-beta -mediated growth inhibition. Thus, in line with the current view that the diversity of TGF-beta responses is not so much a consequence of the use of different signaling pathways but caused by different ways of reading the output from the same basic pathway, we propose that the telomerase status of a cell creates a gene expression pattern that determines how cells read growth inhibitory signals, among them signals propagated through the TGF-beta pathway.
Keywords: repeat sample
Contributor(s) Geserick C, González-Suárez E, Klatt P, Blasco MA
Citation(s) 16501597
Submission date May 19, 2005
Last update date Jan 08, 2019
Contact name Peter Klatt
Phone ++34-917328036
Organization name Spanish National Cancer Center (CNIO)
Department Molecular Oncology Program
Street address
City Madrid
ZIP/Postal code 28029
Country Spain
Platforms (1)
GPL339 [MOE430A] Affymetrix Mouse Expression 430A Array
Samples (4)
GSM51913 control 1
GSM51914 control 2
GSM51915 mTert 1
BioProject PRJNA92187

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Supplementary file Size Download File type/resource
GSE2684_RAW.tar 40.5 Mb (http)(custom) TAR (of CEL, CHP, EXP, RPT, TXT)
Processed data provided as supplementary file

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