Transforming growth factor beta 1 stimulates vascular endothelial growth factor gene transcription in human cholangiocellular carcinoma cells
| Autor: | Christoph, Benckert, Sven, Jonas, Thorsten, Cramer, Zofia, Von Marschall, Georgia, Schäfer, Michael, Peters, Karola, Wagner, Cornelia, Radke, Bertram, Wiedenmann, Peter, Neuhaus, Michael, Höcker, Stefan, Rosewicz |
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| Rok vydání: | 2003 |
| Předmět: |
Transcriptional Activation
Vascular Endothelial Growth Factor A Lymphokines Binding Sites Transcription Genetic Sp1 Transcription Factor Vascular Endothelial Growth Factors Endothelial Growth Factors Immunohistochemistry Cholangiocarcinoma DNA-Binding Proteins Transforming Growth Factor beta1 Bile Ducts Intrahepatic Receptors Vascular Endothelial Growth Factor Sp3 Transcription Factor Bile Duct Neoplasms Transforming Growth Factor beta Tumor Cells Cultured Humans Intercellular Signaling Peptides and Proteins Promoter Regions Genetic Receptors Transforming Growth Factor beta In Situ Hybridization Transcription Factors |
| Zdroj: | Cancer research. 63(5) |
| ISSN: | 0008-5472 |
| Popis: | The expression pattern and functional interaction of proangiogenic factors in human cholangiocellular carcinoma (CCC) have not been fully defined. We therefore investigated the expression of vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-beta 1 as well as their respective receptors in human CCC tumor samples and further analyzed their functional interaction in vitro. Expression of VEGF, TGF-beta 1, and their receptors was examined by immunohistochemistry, in situ hybridization, quantitative competitive reverse transcription-PCR, and ELISA. VEGF promoter analysis and identification of transcription factors involved in promoter regulation were investigated using transient transfection and electrophoretic mobility shift assays. We observed strong expression of VEGF in CCC tumor cells and localization of VEGF receptors 1 and 2 in endothelial cells; in addition, coexpression of TGF-beta 1 and its receptors in tumor cells suggests a possible functional interaction between both cytokines. In vitro studies confirmed a paracrine/autocrine stimulation of VEGF by TGF-beta 1 at a transcriptional level. Additional molecular studies using 5' deletion and mutational analysis of the human VEGF promoter revealed that TGF-beta 1 stimulates VEGF through Sp1-dependent transcriptional activation. These data suggest that overexpression and functional interaction of TGF-beta 1 and VEGF might contribute to the "angiogenic switch" and the malignant phenotype in human CCC. |
| Databáze: | OpenAIRE |
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