TGF-beta and cancer: is Smad3 a repressor of hTERT gene?

Abstract:

:Transforming growth factor beta (TGF-beta) carries out tumor suppressor activity in epithelial and lymphoid cells, whereas telomerase is required for most cancers. Although the molecular mechanisms by which TGF-beta acts as a tumor suppressor are yet to be fully established, a link between TGFb and its tumor suppressor activity by telomerase has been suggested. Recently, we have noted a novel mode of action for TGF-beta through which human telomerase reverse transcriptase (hTERT) gene is repressed in immortal and neoplastic cells, confirming that one of the mechanisms underlying TGF-beta suppression of tumor growth may be through inhibiting hTERT gene transcription. Moreover, the inhibition of hTERT gene by TGF-beta suggests a cis action of the TGF-beta signaling molecule Smad3 on hTERT promoter directly. This article examines our current understanding and investigation of TGF-beta regulation of telomerase activity, and presents a model in which Smad3 participates in regulating hTERT gene transcription by acting as a repressor directly. Engineering the interface between Smad3 and hTERT gene may lead to a new strategy to inhibit telomerase activity in cancer.

journal_name

Cell Res

journal_title

Cell research

authors

Li H,Xu D,Toh BH,Liu JP

doi

10.1038/sj.cr.7310023

keywords:

subject

Has Abstract

pub_date

2006-02-01 00:00:00

pages

169-73

issue

2

eissn

1001-0602

issn

1748-7838

pii

7310023

journal_volume

16

pub_type

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