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E-GEOD-2684 - Transcription profiling of mouse embryonic fibroblasts overexpressing mTert

Status
Released on 12 June 2008, last updated on 2 May 2014
Organism
Mus musculus
Samples (4)
Array (1)
Protocols (3)
Description
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.
Experiment types
transcription profiling by array, compound treatment
Contact
Citation
Expression of mTert in primary murine cells links the growth-promoting effects of telomerase to transforming growth factor-beta signaling. C Geserick, A Tejera, E González-Suárez, P Klatt, M A Blasco. Oncogene 25(31):4310-9 (2006)
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-2684.idf.txt
Sample and data relationshipE-GEOD-2684.sdrf.txt
Raw data (1)E-GEOD-2684.raw.1.zip
Processed data (1)E-GEOD-2684.processed.1.zip
Array designA-AFFY-36.adf.txt
R ExpressionSetE-GEOD-2684.eSet.r
Links