Expression of mTert in primary murine cells links the growth-promoting effects of telomerase to transforming growth factor-beta signaling

Oncogene. 2006 Jul 20;25(31):4310-9. doi: 10.1038/sj.onc.1209465. Epub 2006 Feb 27.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / physiology
  • Gene Expression Profiling
  • Growth Inhibitors / antagonists & inhibitors
  • Growth Inhibitors / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Retroviridae / genetics
  • Signal Transduction / physiology*
  • Telomerase / biosynthesis
  • Telomerase / deficiency
  • Telomerase / genetics
  • Telomerase / physiology*
  • Transduction, Genetic
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / physiology*


  • DNA-Binding Proteins
  • Growth Inhibitors
  • Transforming Growth Factor beta
  • Telomerase