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Reduced expression of transforming growth factor beta type I receptor contributes to the malignancy of human colon carcinoma cells.

Publication ,  Journal Article
Wang, J; Han, W; Zborowska, E; Liang, J; Wang, X; Willson, JK; Sun, L; Brattain, MG
Published in: J Biol Chem
July 19, 1996

Transforming growth factor beta (TGFbeta) type I (RI) and type II (RII) receptors are essential for TGFbeta signal transduction. A human colon carcinoma cell line, designated GEO, is marginally responsive to TGFbeta and expresses a low level of RI mRNA relative to colon carcinoma cells, which are highly responsive to TGFbeta. Hence, the role of RI as a limiting factor for TGFbeta sensitivity and the contribution of low RI levels to the malignant phenotype of GEO cells were examined. Stable transfection of a tetracycline-regulatable rat RI cDNA increased TGFbeta1 binding to RI and resulted in increased growth inhibition by exogenous TGFbeta1. In contrast, although stable transfection of an RII expression vector into the same GEO cells increased TGFbeta1 binding to RII, growth inhibition by exogenous TGFbeta1 was not altered. This indicated that the low level of RI is a limiting factor for the growth-inhibitory effects of TGFbeta in GEO cells. RI-transfected cells were growth-arrested at a lower saturation density than GEO control cells. They also showed reduced growth and clonogenicity in plating efficiency and soft agarose assays, whereas RII-transfected cells did not show any differences from the NEO control cells in these assays. Tetracycline repressed RI expression in transfected cells and reversed the reduction in plating efficiency of RI-transfected clones, confirming that growth effects were due to increased RI expression in transfected cells. TGFbeta1 neutralizing antibody stimulated the proliferation of RI-transfected cells but had little effect on GEO control cells, indicating that increased autocrine-negative TGFbeta activity also resulted from increased RI expression. Tumorigenicity in athymic nude mice was significantly delayed in RI-transfected cells. These results indicate that low RI expression can be a limiting factor for response to exogenous TGFbeta, as well as TGFbeta autocrine-negative activity, and that reduction of RI expression can contribute to malignant progression.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

July 19, 1996

Volume

271

Issue

29

Start / End Page

17366 / 17371

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transforming Growth Factor beta
  • Transfection
  • Transcription, Genetic
  • Tetracycline
  • Recombinant Proteins
  • Receptors, Transforming Growth Factor beta
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptor, Transforming Growth Factor-beta Type I
  • Rats
 

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Wang, J., Han, W., Zborowska, E., Liang, J., Wang, X., Willson, J. K., … Brattain, M. G. (1996). Reduced expression of transforming growth factor beta type I receptor contributes to the malignancy of human colon carcinoma cells. J Biol Chem, 271(29), 17366–17371. https://doi.org/10.1074/jbc.271.29.17366
Wang, J., W. Han, E. Zborowska, J. Liang, X. Wang, J. K. Willson, L. Sun, and M. G. Brattain. “Reduced expression of transforming growth factor beta type I receptor contributes to the malignancy of human colon carcinoma cells.J Biol Chem 271, no. 29 (July 19, 1996): 17366–71. https://doi.org/10.1074/jbc.271.29.17366.
Wang J, Han W, Zborowska E, Liang J, Wang X, Willson JK, et al. Reduced expression of transforming growth factor beta type I receptor contributes to the malignancy of human colon carcinoma cells. J Biol Chem. 1996 Jul 19;271(29):17366–71.
Wang, J., et al. “Reduced expression of transforming growth factor beta type I receptor contributes to the malignancy of human colon carcinoma cells.J Biol Chem, vol. 271, no. 29, July 1996, pp. 17366–71. Pubmed, doi:10.1074/jbc.271.29.17366.
Wang J, Han W, Zborowska E, Liang J, Wang X, Willson JK, Sun L, Brattain MG. Reduced expression of transforming growth factor beta type I receptor contributes to the malignancy of human colon carcinoma cells. J Biol Chem. 1996 Jul 19;271(29):17366–17371.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

July 19, 1996

Volume

271

Issue

29

Start / End Page

17366 / 17371

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transforming Growth Factor beta
  • Transfection
  • Transcription, Genetic
  • Tetracycline
  • Recombinant Proteins
  • Receptors, Transforming Growth Factor beta
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptor, Transforming Growth Factor-beta Type I
  • Rats