Genes down-regulated in MEF cells (embryonic fibroblasts) with TERT [GeneID=7015] knockout, after expression of the gene off a retroviral vector.
Full description or 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.
Collection
M2: Curated CGP: Chemical and Genetic Perturbations
Source publication
Pubmed 16501597 Authors: Geserick C,Tejera A,González-Suárez E,Klatt P,Blasco MA