Autocrine transforming growth factor beta suppresses telomerase activity and transcription of human telomerase reverse transcriptase in human cancer cells

Because autocrine transforming growth factor beta (TGF-beta) can suppress c arcinogenesis, which is often associated with telomerase activation, we stu died whether autocrine TGF-beta inhibits telomerase activity. Restoration o f autocrine TGF-beta activity in human colon carcinoma HCT116 cells after r eexpression 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 dom inant negative RII without the cytoplasmic domain (Delta RII) in human brea st 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 tr anscription because exogenous TGF-beta treatment of MCF-7 cells transiently transfected with a hTERT promoter-reporter construct significantly repress ed the hTERT promoter activity in a dose-dependent manner. Furthermore, the hTERT promoter activity was significantly decreased in HCT116 RII cells an d increased in MCF-7 Delta RII cells when compared with their respective co ntrols. Therefore, autocrine TGF-beta appears to target hTERT promoter to i nhibit telomerase activity.