Ligand induced upregulation of the type II transforming growth factor (TGF-beta) receptor enhances TGF-beta responsiveness in COLO-357 cells

Pancreas. 1999 May;18(4):364-70. doi: 10.1097/00006676-199905000-00006.


The effects of transforming growth factor (TGF)-beta 1 on type I and type II TGF-beta receptor (T beta RI and T beta RII) expression were examined in five pancreatic cancer cell lines. In contrast to its actions in COLO-357, a TGF-beta-sensitive pancreatic cancer cell line, TGF-beta 1 did not significantly alter TGF-beta receptor expression in either the TGF-beta-sensitive BXPC-3 and PANC-1 cells or in the TGF-beta-resistant CAPAN-1 and T3M4 cells. Neutralizing anti-T beta RII antibodies blocked TGF-beta 1-dependent signaling in COLO-357 cells but exhibited an attenuated effect in COLO-357 cells preincubated with TGF-beta 1 for 48 h. Basal T beta RII expression levels were comparable in all five cell lines examined. In contrast, COLO-357 cells and BX-PC-3 cells expressed relatively high basal levels of T beta RI. However, COLO-357 cells harbored a normal Smad4 gene, whereas BX-PC-3 cells exhibited a complete deletion of this gene. We conclude that the TGF-beta 1-induced T beta RII upregulation serves to enhance TGF-beta 1 responsiveness in COLO-357 cells, and that this upregulation requires the presence of adequate levels of T beta RI and T beta RII, and a functional Smad4 gene product. Our findings also indicate that TGF-beta 1 may inhibit pancreatic cancer cell growth via a Smad4-independent pathway.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Division
  • DNA-Binding Proteins / genetics
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mutation
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Receptors, Transforming Growth Factor beta / genetics*
  • Smad4 Protein
  • Trans-Activators / genetics
  • Transfection
  • Transforming Growth Factor beta / pharmacology*
  • Tumor Cells, Cultured


  • DNA-Binding Proteins
  • Receptors, Transforming Growth Factor beta
  • SMAD4 protein, human
  • Smad4 Protein
  • Trans-Activators
  • Transforming Growth Factor beta