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

H. Yang, S. Kyo, M. Takatura, L. Sun

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

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 languageEnglish (US)
Pages (from-to)119-127
Number of pages9
JournalCell Growth and Differentiation
Volume12
Issue number2
StatePublished - 2001

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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