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  • Title: Autocrine transforming growth factor beta suppresses telomerase activity and transcription of human telomerase reverse transcriptase in human cancer cells.
    Author: Yang H, Kyo S, Takatura M, Sun L.
    Journal: Cell Growth Differ; 2001 Feb; 12(2):119-27. PubMed ID: 11243466.
    Abstract:
    Because autocrine transforming growth factor beta (TGF-beta) can suppress carcinogenesis, which is often associated with telomerase activation, we studied whether autocrine TGF-beta inhibits telomerase activity. Restoration of autocrine TGF-beta 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-beta activity with a dominant negative RII without the cytoplasmic domain (deltaRII) 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-beta 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 deltaRII cells when compared with their respective controls. Therefore, autocrine TGF-beta appears to target hTERT promoter to inhibit telomerase activity.
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