Resistance to transforming growth factor-beta occurs in the presence of normal smad activation

David H. Berger, Xin Hua Feng, Jun Yao, Debabrata Saha, R. Daniel Beauchamp, Xia Lin

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Background. Resistance to the growth inhibitory actions of transforming growth factor-beta (TGF-β) is common in human cancers. This resistance can be a result of decreased expression of TGF-β receptors. Downregulation of c-Myc by TGF-β is critical for TGF-β-mediated growth inhibition. In this study we hypothesized that decreased TGF-β receptor expression leads to reduced Smad signaling and overexpression of c-Myc in intestinal epithelial (RIE) and transformed intestinal epithelial cells (RIE-Tr) cells. Methods. RIE (TGF-β-sensitive) and RIE-Tr (TGF-β-resistant) cells were treated with and without fetal bovine serum and TGF-β. Western blot analysis was performed to detect levels of c-Myc, Smad2, Smad4, and phosphorylated Smad2 in RIE and RIE-Tr cells. Smad complex formation was analyzed by immunoprecipitation-coupled Western blotting. Results. c-Myc is overexpressed in RIE-Tr cells. TGF-β-mediated downregulation of c-Myc is abrogated in RIE-Tr cells. Smad expression and activation is normal in RIE-Tr cells. We found that Smad2, Smad4, and Smad6 expression remained constant in RIE and RIE-Tr cells with or without serum or TGF-β treatment. In addition, TGF-β induced similar Smad2 phosphorylation and Smad complex formation in both RIE and RIE-Tr cells. Conclusions. Our data demonstrate that Smad signaling is preserved in the face of decreased TGF-β receptor levels. We also demonstrate that Smad signaling is not sufficient for TGF-β-mediated c-Myc repression.

Original languageEnglish (US)
Pages (from-to)310-316
Number of pages7
Issue number2
StatePublished - Aug 2002

ASJC Scopus subject areas

  • Surgery


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