TY - JOUR
T1 - Resistance to transforming growth factor-beta occurs in the presence of normal smad activation
AU - Berger, David H.
AU - Feng, Xin Hua
AU - Yao, Jun
AU - Saha, Debabrata
AU - Beauchamp, R. Daniel
AU - Lin, Xia
N1 - Funding Information:
Supported by American Cancer Society AQ·96-09 (D.H.B.), American Cancer Society RPG-00214-01-CCG and National Institutes of Health RO1GM63773 (X-H.F.), National Institutes of Health RO1DK52334 and RO1CA69457 (R.D.B.), and Baylor Startup Funds (X-H.F. and X.L.).
PY - 2002/8
Y1 - 2002/8
N2 - 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.
AB - 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.
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U2 - 10.1067/msy.2002.126097
DO - 10.1067/msy.2002.126097
M3 - Article
C2 - 12219028
AN - SCOPUS:0036676123
SN - 0039-6060
VL - 132
SP - 310
EP - 316
JO - Surgery
JF - Surgery
IS - 2
ER -