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Updated: Sep 29, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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Resistance to transforming growth factor-beta occurs in the presence of normal Smad activation

David H Berger1, Xin-Hua Feng, Jun Yao

  • 1Department of Surgery, The Baylor College of Medicine, Houston, Tex, USA.

Surgery
|September 10, 2002
PubMed
Abstract

Insights

Transforming growth factor-beta (TGF-beta) resistance in cancer is linked to c-Myc overexpression. Despite normal Smad signaling, TGF-beta fails to repress c-Myc in resistant cells, suggesting Smad pathway sufficiency is not the sole factor.

Area of Science:

  • Cell biology
  • Cancer research
  • Molecular signaling

Background:

  • Resistance to transforming growth factor-beta (TGF-beta) is prevalent in human cancers, often due to reduced TGF-beta receptor expression.
  • TGF-beta's downregulation of c-Myc is crucial for its growth inhibitory effects, and its loss contributes to cancer progression.

Purpose of the Study:

  • To investigate the hypothesis that decreased TGF-beta receptor expression leads to impaired Smad signaling and elevated c-Myc levels.
  • To examine the relationship between TGF-beta receptor levels, Smad signaling, and c-Myc regulation in intestinal epithelial cells.

Main Methods:

  • Western blot analysis was used to quantify c-Myc, Smad2, Smad4, and phosphorylated Smad2 levels.
  • Immunoprecipitation-coupled Western blotting assessed Smad complex formation.
  • Treated TGF-beta-sensitive (RIE) and TGF-beta-resistant (RIE-Tr) cells with and without serum and TGF-beta.

Main Results:

  • c-Myc was overexpressed in RIE-Tr cells, and TGF-beta's ability to downregulate c-Myc was lost.
  • Smad2, Smad4, and Smad6 expression levels remained consistent across cell types and treatments.
  • TGF-beta induced comparable Smad2 phosphorylation and Smad complex formation in both RIE and RIE-Tr cells.

Conclusions:

  • Smad signaling pathways are functional and unaffected by reduced TGF-beta receptor levels.
  • Normal Smad signaling is insufficient to mediate TGF-beta-induced c-Myc repression in cancer cells.

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