Because autocrine transforming growth factor β (TGF-β) can suppress carcinogenesis, which is often associated with telomerase activation, we studied whether autocrine TGF-β inhibits telomerase activity. Restoration of autocrine TGF-β activity in human colon carcinoma HCT116 cells after reexpression of its type II receptor (RII) led to a significant reduction of telomerase activity and the mRNA level of telomerase reverse transcriptase (hTERT), whereas suppression of the autocrine TGF-β activity with a dominant negative RII without the cytoplasmic domain (δRII) in human breast cancer MCF-7 cells led to a significant increase of telomerase activity and hTERT mRNA level. This appears to be due to repression of hTERT mRNA transcription because exogenous TGF-β treatment of MCF-7 cells transiently transfected with a hTERT promoter-reporter construct significantly repressed the hTERT promoter activity in a dose-dependent manner. Furthermore, the hTERT promoter activity was significantly decreased in HCT116 RII cells and increased in MCF-7 δRII cells when compared with their respective controls. Therefore, autocrine TGF-β appears to target hTERT promoter to inhibit telomerase activity.
|Original language||English (US)|
|Number of pages||9|
|Journal||Cell Growth and Differentiation|
|State||Published - 2001|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology