¹Department of Immunology, Molecular Signaling Laboratory, Monash University, Melbourne, Australia

Correspondence: He Li, Department of Immunology, Monash Medical School, AMREP, Commercial Road, Prahran, Victoria 3181, Australia. Tel.: 61-3-99030715; Fax: 61-3-99030018; E-mail: he.li@med.monash.edu.au

Abstract

Transforming growth factor (TGF-) carries out tumor suppressor activity in epithelial and lymphoid cells, whereas telomerase is required for most cancers. Although the molecular mechanisms by which TGF- 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- through which human telomerase reverse transcriptase (hTERT) gene is repressed in immortal and neoplastic cells, confirming that one of the mechanisms underlying TGF- suppression of tumor growth may be through inhibiting hTERT gene transcription. Moreover, the inhibition of hTERT gene by TGF- suggests a cis action of the TGF- signaling molecule Smad3 on hTERT promoter directly. This article examines our current understanding and investigation of TGF- 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.