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Department of Surgery, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229 [H. Y., L. S.], and Department of Obstetrics and Gynecology, Kanazawa University, School of Medicine, Ishikawa 920-0934, Japan [S. K., M. T.]
Because autocrine transforming growth factor ß (TGF-ß) can
suppress carcinogenesis, which is often associated with telomerase
activation, we studied whether autocrine TGF-ß inhibits telomerase
activity. Restoration of autocrine TGF-ß 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-ß activity with a dominant negative RII without
the cytoplasmic domain (
RII) 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-ß 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 RII cells when
compared with their respective controls. Therefore, autocrine TGF-ß
appears to target hTERT promoter to inhibit telomerase activity.
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