Smad6 suppresses TGF-beta-induced growth inhibition in COLO-357 pancreatic cancer cells and is overexpressed in pancreatic cancer

Biochem Biophys Res Commun. 1999 Feb 16;255(2):268-73. doi: 10.1006/bbrc.1999.0171.


Transforming growth factor (TGF)-beta signaling is initiated by heterodimerization of TGF-beta receptor type I (TbetaRI) and type II (TbetaRII). Subsequently, the signal is transduced via Smad proteins, which upon phosphorylation and heterodimerization translocate to the nucleus and regulate gene transcription. Smad6 functions as an intracellular antagonist of TGF-beta signaling. In the present study we demonstrate that Smad6 is overexpressed in vivo in human pancreatic cancer cells. We also show that stable transfection of a full-length Smad6 construct into COLO-357 pancreatic cancer cells abrogates TGF-beta1 induced growth inhibition, and leads to enhanced anchorage-independent growth. Thus, enhanced expression of the TGF-beta signaling inhibitor Smad6 in pancreatic cancer may present a novel mechanism of TGF-beta resistance, which might have the potential to enhance the transformed phenotype of human cancer cells.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents / antagonists & inhibitors*
  • Antineoplastic Agents / pharmacology
  • Blotting, Northern
  • Cell Division / drug effects
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Female
  • Growth Inhibitors / antagonists & inhibitors*
  • Growth Inhibitors / pharmacology
  • Humans
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / chemistry
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Smad6 Protein
  • Trans-Activators / biosynthesis*
  • Trans-Activators / genetics
  • Trans-Activators / physiology*
  • Transforming Growth Factor beta / pharmacology*
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • DNA-Binding Proteins
  • Growth Inhibitors
  • SMAD6 protein, human
  • Smad6 Protein
  • Trans-Activators
  • Transforming Growth Factor beta