1. Down-regulation of TGF-β receptors in human colorectal cancer: implications for cancer development.
- Author
-
Matsushita, M, Matsuzaki, K, Date, M, Watanabe, T, Shibano, K, Nakagawa, T, Yanagitani, S, Amoh, Y, Takemoto, H, Ogata, N, Yamamoto, C, Kubota, Y, Seki, T, Inokuchi, H, Nishizawa, M, Takada, H, Sawamura, T, and Okamura, A
- Subjects
COLON cancer ,CANCER cells ,MESENCHYME - Abstract
Many colorectal cancer cells are resistant to the anti-proliferative effects of transforming growth factor-β (TGF-β). TGF-β also acts as paracrine factor from cancer cells on their mesenchymal cells. The aim of this study was to examine the expression of TGF-β 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-β[SUB1], type I and type II receptor mRNA and immunohistochemical staining of TGF-β[SUB1] were performed using 11 human colorectal adenomas, 22 colorectal cancers and ten normal colorectal mucosas as control. TGF-β receptor mRNAs were expressed mainly by normal colorectal epithelial cells and adenoma. However, mRNAs for TGF-β receptors were only faintly, if at all, expressed in eight of 22 human colorectal cancers. In addition, intense signals of TGF-β[SUB1] mRNA and the protein were detected in all colorectal cancers. TGF-β receptor mRNAs and TGF-β[SUB1] 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-β stimulation. The escape of human colon cancer from TGF-β -mediated growth inhibition by down-regulation of TGF-β receptors as well as the effects of TGF-β on stroma formation and angiogenesis indicate a possible role for TGF-β in the progression of colon cancer in an intact host. [ABSTRACT FROM AUTHOR]
- Published
- 1999
- Full Text
- View/download PDF