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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

1999-04

AUTHORS

M Matsushita, K Matsuzaki, M Date, T Watanabe, K Shibano, T Nakagawa, S Yanagitani, Y Amoh, H Takemoto, N Ogata, C Yamamoto, Y Kubota, T Seki, H Inokuchi, M Nishizawa, H Takada, T Sawamura, A Okamura, K Inoue

ABSTRACT

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. More... »

PAGES

6690339

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.bjc.6690339

DOI

http://dx.doi.org/10.1038/sj.bjc.6690339

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1032312687

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/10389996


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