Expression of mTert in primary murine cells links the growth-promoting effects of telomerase to transforming growth factor-beta signaling.
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.
Geserick
C
C
Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center (CNIO), Melchor Fernández Almagro, Madrid, Spain.
Tejera
A
A
González-Suárez
E
E
Klatt
P
P
Blasco
M A
MA
D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D020869:Gene Expression Profiling; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012190:Retroviridae / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D019098:Telomerase / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014161:Transduction, Genetic; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000502:physiology*
D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; D016212:Transforming Growth Factor beta; D019098:Telomerase