TGF-β repression of Id2 induces apoptosis in gut epithelial cells

Y. Cao, X. Liu, W. Zhang, X. Deng, H. Zhang, Y. Liu, L. Chen, E. A. Thompson, C. M. Townsend, T. C. Ko

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Transforming growth factor-β (TGF-β) regulates epithelial tissue homeostasis by activating processes that control cell cycle arrest, differentiation and apoptosis. Disruption of the TGF-β signaling pathway often occurs in colorectal cancers. Earlier, we have shown that TGF-β induces apoptosis through the transcription factor Smad3. Affymetrix oligonucleotide microarrays were used to identify TGF-β/Smad3 target genes that regulate apoptosis in rat intestinal epithelial cells (RIE-1). We found that TGF-β repressed the expression of the inhibitor of differentiation (Id) gene family. Knockdown of Id1 and Id2 gene expression induced apoptosis in RIE-1 cells, whereas overexpression of Id2 attenuated TGF-β-induced apoptosis. TranSignal Protein/DNA arrays were used to identify the hypoxia-inducing factor-1 (HIF-1) as a downstream target of TGF-β. HIF-1 is a basic helix-loop-helix protein, and overexpression of Id2 blocked HIF-1 activation by TGF-β. Furthermore, knockdown of HIF-1 blocked TGF-β-induced apoptosis. Thus, we have identified HIF-1 as a novel mediator downstream of Id2 in the pathway of TGF-β-induced apoptosis.

Original languageEnglish (US)
Pages (from-to)1089-1098
Number of pages10
JournalOncogene
Volume28
Issue number8
DOIs
StatePublished - Feb 26 2009

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Keywords

  • Affymetrix oligonucleotide microarrays
  • Apoptosis
  • Hypoxia-inducing factor
  • Inhibitor of differentiation
  • TranSignal Protein/DNA arrays

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Cao, Y., Liu, X., Zhang, W., Deng, X., Zhang, H., Liu, Y., Chen, L., Thompson, E. A., Townsend, C. M., & Ko, T. C. (2009). TGF-β repression of Id2 induces apoptosis in gut epithelial cells. Oncogene, 28(8), 1089-1098. https://doi.org/10.1038/onc.2008.456