TGF-beta signaling in colon cancer cells

World J Surg. 2005 Mar;29(3):306-11. doi: 10.1007/s00268-004-7813-6.


Transforming growth factor-betas (TGF-betas), cytokines expressed in the colon, play important roles as tumor suppressors and tumor promoters during colorectal carcinogenesis. TGF-beta signaling pathway involves activation of Smad2 and Smad3 by the type I receptor and formation of Smad2/3/4 heteromeric complexes that enter the nucleus to regulate transcription. Most human colorectal cancers are resistant to the tumor suppressor effects of TGF-beta, and a subset of human colorectal cancers have mutations in Smad2 and Smad4. The purpose of this study was to determine whether Smads are required for TGF-beta signaling in colon cancer cells. First, we selected a colon cancer cell line (MC-26) that has a functional TGF-beta signaling pathway. We found that MC-26 cells expressed Smad2, Smad3, and Smad4 mRNAs by reverse transeription-polymerase chain reaction and confirmed that the TGF-beta signaling pathway is functional using a transient transfection assay with 3TP-Lux reporter plasmid. TGF-beta also inhibited cell growth and induced apoptosis in MC-26 cells. When MC-26 cells were transiently transfected with dominant-negative carboxyl-terminal truncation mutants of Smad2, Smad3, and Smad4, TGF-beta-induced 3TP-Lux reporter activity was significantly reduced, suggesting that Smad2, Smad3, and Smad4 are attractive novel therapeutic targets for regulating TGF-beta signaling in colorectal cancers. Because MC-26 cells express TGF-beta activated Smads, have a functional TGF-beta signaling pathway, and are sensitive to the growth inhibitory and apoptotic effects of TGF-beta, they can serve as an excellent model to examine TGF-beta signaling in colorectal cancers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Mice
  • RNA, Messenger / metabolism
  • Signal Transduction
  • Smad Proteins
  • Smad2 Protein
  • Smad3 Protein
  • Smad4 Protein
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transforming Growth Factor beta / physiology*


  • DNA-Binding Proteins
  • RNA, Messenger
  • Smad Proteins
  • Smad2 Protein
  • Smad2 protein, mouse
  • Smad3 Protein
  • Smad3 protein, mouse
  • Smad4 Protein
  • Trans-Activators
  • Transforming Growth Factor beta