Bone morphogenetic protein-4 is overexpressed in colonic adenocarcinomas and promotes migration and invasion of HCT116 cells
| Autor: | Wancai Yang, Ryouji Makizumi, Huali Dong, Thanjavur S. Ravikumar, Haiyun Deng, Weng Lang Yang |
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| Rok vydání: | 2007 |
| Předmět: |
animal structures
Cell Survival Protein Array Analysis Apoptosis Bone Morphogenetic Protein 4 Adenocarcinoma Biology Bone Morphogenetic Protein Receptors Type II Transfection Cell morphology medicine.disease_cause Bone morphogenetic protein Polymerase Chain Reaction Metastasis Intestinal mucosa Cell Movement Computer Systems Cell Line Tumor medicine Humans Bone morphogenetic protein receptor RNA Messenger Intestinal Mucosa Bone Morphogenetic Protein Receptors Type I Liver Neoplasms Cell Biology medicine.disease Immunohistochemistry Urokinase-Type Plasminogen Activator Up-Regulation Bone morphogenetic protein 4 Bone Morphogenetic Proteins Colonic Neoplasms embryonic structures Immunology Cancer research Carcinogenesis |
| Zdroj: | Experimental Cell Research. 313:1033-1044 |
| ISSN: | 0014-4827 |
| DOI: | 10.1016/j.yexcr.2006.12.020 |
| Popis: | Bone morphogenetic protein (BMP), a member of the TGF-beta superfamily, is involved in development, morphogenesis, cell proliferation and apoptosis. Dysregulation of BMP signaling has been suggested in tumorigenesis. In an analysis of human colon normal mucosa and tumors at different stages by immunohistochemistry, we observed that the intensity of BMP-4 staining in late-adenocarcinomas was stronger than that in normal mucosa and adenomas, while there was no difference in the staining of its receptors (BMPR-IA and BMPR-II) at all stages. The up-regulation of BMP-4 was further validated in another panel of tumor tissues by real-time RT-PCR, showing that BMP-4 mRNA levels in primary colonic carcinomas with liver metastasis were significantly higher than that in the matched normal mucosa. In order to understand the functional relevance of BMP-4 expression in colon cancer progression, BMP-4-overexpressing cell clones were generated from HCT116 cells. Overexpression of BMP-4 did not affect the HCT116 cell growth. The cells overexpressing BMP-4 became resistant to serum-starvation-induced apoptosis and exhibited enhanced migration and invasion characteristics. Overexpression of BMP-4 changed cell morphology to invasive spindle phenotype and induced the expression and activity of urokinase plasminogen activator (uPA). These results indicate that BMP-4 confers invasive phenotype during progression of colon cancer. |
| Databáze: | OpenAIRE |
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