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

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

M Matsushita 1, K Matsuzaki 1, M Date 1, T Watanabe 1, K Shibano 1, T Nakagawa 1, S Yanagitani 1, Y Amoh 1, H Takemoto 1, N Ogata 2, C Yamamoto 2, Y Kubota 1, T Seki 1, H Inokuchi 3, M Nishizawa 4, H Takada 5, T Sawamura 1, A Okamura 6
PMCID: PMC2362997  PMID: 10389996

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-β1, type I and type II receptor mRNA and immunohistochemical staining of TGF-β1 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-β1 mRNA and the protein were detected in all colorectal cancers. TGF-β receptor mRNAs and TGF-β1 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. © 1999 Cancer Research Campaign

Keywords: TGF-β; TGF-β; receptor; Smad, colorectal cancer; colorectal adenoma

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Selected References

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