The TGFβ inducible early gene plays a central role in the anti-proliferative response to TGFβ

Steven A. Johnsen, Malayannan Subramaniam, Katharina E. Effenberger, Thomas C. Spelsberg

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Signaling through the Transforming Growth Factor-β (TGFβ)/Smad pathway plays an important role in a variety of cellular processes including the control of cellular proliferation and oncogenesis. The TGFβ Inducible Early Gene (TIEG) is a primary response gene for TGFβ which controls the activity of the Smad pathway. In addition, studies from our laboratory have demonstrated that TIEG expression is lost during the progression of breast cancer. In the present study we utilized a tetracycline inducible TIEG overexpressing breast cancer cell line and TIEG null mouse embryo fibroblasts (MEFs) to establish whether TIEG plays a central role in eliciting the anti-proliferative effects of TGFβ. We demonstrate that, similar to TGFβ treatment, TIEG overexpression significantly decreases cellular proliferation. Consistent with a role in regulating cellular proliferation, TIEG overexpression increases the expression of the cyclin dependent kinase inhibitor p21. Interestingly, while cellular proliferation of wild-type MEFs is inhibited by TGFβ, proliferation of TIEG null MEFs is stimulated by TGFβ. Furthermore, TIEG null MEF cells display a decrease in Smad dependent transcription with a concomitant prolonged increase in Smad/expression compared to wild-type cells. These data strongly suggest that TIEG plays a central role in the anti-proliferative response to TGFβ and may explain how a loss of TIEG expression contributes to the development of cancer.

Original languageEnglish (US)
Pages (from-to)29-35
Number of pages7
JournalSignal Transduction
Volume4
Issue number1-2
DOIs
StatePublished - Sep 14 2004

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Keywords

  • Breast cancer
  • Cellular proliferation
  • Smad
  • TGF-beta
  • TIEG
  • Transcription factors

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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