Basic-liver, pancreas, and biliary tractActivin A stimulates vascular endothelial growth factor gene transcription in human hepatocellular carcinoma cells☆
Section snippets
Materials
The following were purchased: Dulbecco’s modified Eagle medium and phosphate-buffered saline (Gibco, Berlin, Germany); UltraCulture medium (BioWhittaker, Verviers, Belgium); fetal calf serum, trypsin/ethylenediaminetetraacetic acid, penicillin, and streptomycin (Biochrom, Berlin, Germany); RNAzol B (Wak-Chemie Medical, Bad Soden, Germany); Thermus aquaticus DNA polymerase and PCR Nucleotide Mix (Roche Diagnostics, Indianapolis, IN); DNA molecular size markers, oligodeoxythymidylic acid residues
Expression of activin A and activin receptors in hepatocellular carcinoma
To evaluate the postulated role of activin A in regulation of VEGF gene expression, we initially analyzed the expression of VEGF in 9 surgically resected human HCC samples. Using a polyclonal antibody specific for hVEGF, we consistently observed strong VEGF expression over HCC cells in all tumor specimens tested (Figure 1A). To investigate the potential interaction of VEGF with activin A, we next characterized the expression pattern of activin A and its receptors. Immunohistochemical analysis
Discussion
The pivotal role of VEGF in tumor angiogenesis and, thus, the propagation and metastasis of HCC is supported by several lines of evidence: (1) expression of the VEGF/VEGF-R system is up-regulated in HCC,13, 14 (2) hepatocellular overexpression of VEGF is inversely correlated with the prognosis and survival of HCC patients,43, 44 and (3) inhibition of VEGF has successfully been used to block angiogenesis and restrain HCC cell growth and metastases in a variety of preclinical models.45, 46
Acknowledgements
The authors thank G. Finkenzeller (GeneScan AG, Freiburg, Germany), G. Suske (Institut für Molekularbiologie und Tumorforschung, Marburg, Germany), and R. Derynck (Department of Growth and Development and Anatomy, and Programs in Cell Biology and Developmental Biology, University of California, San Francisco) for generous gifts of plasmids.
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S.R. was supported by grants from the Deutsche Krebshilfe, Wilhelm Sander-Stiftung, Deutsche Forschungsgemeinschaft, Berliner Krebsgesellschaft, Else Kröner Fresenius Stiftung, and Sonnenfeld Stiftung.
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K.W. and M.P. contributed equally to this work.