Down-regulation of TGF-β receptors in human colorectal cancer: implications for cancer development
| Autor: | Masanori Matsushita, H Inokuchi, Taiichi Nakagawa, Hideho Takada, Chikako Yamamoto, H Takemoto, Toshihiko Watanabe, Akiharu Okamura, T Sawamura, Shingo Yanagitani, K Shibano, Toshihito Seki, Y Kubota, Nahoko Ogata, Kouichi Matsuzaki, Masataka Date, Mikio Nishizawa, Kyoichi Inoue, Yasuo Amoh |
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| Jazyk: | angličtina |
| Rok vydání: | 1999 |
| Předmět: |
TGF-β
Adenoma Adult Male Cancer Research Pathology medicine.medical_specialty Deleted in Colorectal Cancer Colorectal cancer Angiogenesis receptor Down-Regulation Mouse model of colorectal and intestinal cancer Paracrine signalling Transforming Growth Factor beta Smad colorectal cancer medicine Humans RNA Messenger In Situ Hybridization Aged colorectal adenoma biology Cancer Regular Article Transforming growth factor beta Middle Aged medicine.disease Blotting Northern Immunohistochemistry Oncology Cancer cell Cancer research biology.protein Female Colorectal Neoplasms Receptors Transforming Growth Factor beta |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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