Down-regulation of TGF-beta receptors in human colorectal cancer: implications for cancer development

Br J Cancer. 1999 Apr;80(1-2):194-205. doi: 10.1038/sj.bjc.6690339.


Many colorectal cancer cells are resistant to the anti-proliferative effects of transforming growth factor-beta (TGF-beta). TGF-beta also acts as paracrine factor from cancer cells on their mesenchymal cells. The aim of this study was to examine the expression of TGF-beta and its receptors in human colorectal cancer tissue and determine any relationship with cancer growth. In situ hybridization and Northern blot hybridization detection of TGF-beta1, type I and type II receptor mRNA and immunohistochemical staining of TGF-beta1 were performed using 11 human colorectal adenomas, 22 colorectal cancers and ten normal colorectal mucosas as control. TGF-beta receptor mRNAs were expressed mainly by normal colorectal epithelial cells and adenoma. However, mRNAs for TGF-beta receptors were only faintly, if at all, expressed in eight of 22 human colorectal cancers. In addition, intense signals of TGF-beta1 mRNA and the protein were detected in all colorectal cancers. TGF-beta receptor mRNAs and TGF-beta1 protein were also distributed in fibroblasts and endothelial cells in the interstitium. Moreover, Smad 4 protein was translocated to nucleus in primarily cultured adenoma cells, but not in cancer cells after TGF-beta stimulation. The escape of human colon cancer from TGF-beta-mediated growth inhibition by down-regulation of TGF-beta receptors as well as the effects of TGF-beta on stroma formation and angiogenesis indicate a possible role for TGF-beta in the progression of colon cancer in an intact host.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / metabolism*
  • Adenoma / pathology
  • Adult
  • Aged
  • Blotting, Northern
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Down-Regulation
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Male
  • Middle Aged
  • RNA, Messenger / analysis
  • Receptors, Transforming Growth Factor beta / biosynthesis*
  • Transforming Growth Factor beta / metabolism


  • RNA, Messenger
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta