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Cell Growth & Differentiation Vol. 12, 119-127, February 2001
© 2001 American Association for Cancer Research

Autocrine Transforming Growth Factor ß Suppresses Telomerase Activity and Transcription of Human Telomerase Reverse Transcriptase in Human Cancer Cells1

Hua Yang, Satoru Kyo, Masahiro Takatura and LuZhe Sun2

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 ({Delta}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 {Delta}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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Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 2001 by the American Association of Cancer Research.