Expression of mTert in primary murine cells links the growth-promoting effects of telomerase to transforming growth factor-beta signaling.
Oncogene, 2006/7/20;25(31):4310-9.
Geserick C[1], Tejera A, González-Suárez E, Klatt P, Blasco MA
Affiliations
PMID: 16501597
Impact factor: 8.756
Abstract
Here, we show that ectopic expression of the catalytic subunit of mouse telomerase (mTert) confers a growth advantage to primary murine embryonic fibroblasts (MEFs), which have very long telomeres, as well as facilitates their spontaneous immortalization and increases their colony-forming capacity upon activation of oncogenes. We demonstrate that these telomere length-independent growth-promoting effects of mTert overexpression require catalytically active mTert, as well as the formation of mTert/Terc complexes. The gene expression profile of mTert-overexpressing MEFs indicates that telomerase enhances growth in these cells through the repression of growth-inhibiting genes of the transforming growth factor-beta (TGF-beta) signaling network. We functionally validate this result by showing that mTert abrogates the growth-inhibitory effect of TGF-beta in MEFs, thus demonstrating that telomerase increments the proliferative potential of primary mouse embryonic fibroblasts by targeting the TGF-beta pathway.
MeSH terms
Animals; Cells, Cultured; DNA-Binding Proteins; Gene Expression Profiling; Growth Inhibitors; Mice; Mice, Inbred C57BL; Mice, Knockout; Retroviridae; Signal Transduction; Telomerase; Transduction, Genetic; Transforming Growth Factor beta
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