Reversion of deregulated expression of vascular endothelial growth factor in human renal carcinoma cells by von Hippel-Lindau tumor suppressor protein.

Abstract	Mutations or loss of both alleles of the von Hippel-Lindau (VHL) tumor suppressor gene has been documented in sporadic renal cell carcinomas and neoplasms that arise in individuals having the VHL syndrome. The well-vascularized phenotype of tumors that form in VHL disease let us consider vascular endothelial growth factor (VEGF) as a mediator of tumor growth in VHL disease. Human renal carcinoma cells that either lacked endogenous wild-type VHL or were transfected with an inactive mutant VHL showed deregulated expression of VEGF on the mRNA and protein level that was reverted by introduction of wild-type VHL. Stimulation of proliferation of endothelial cells by conditioned medium of cells expressing mutant VHL was almost abolished by neutralizing the VEGF. In contrast, expression of basic fibroblast growth factor and of c-myc proto-oncogene was not affected by VHL. Our data suggest VEGF as the key tumor angiogenesis factor in VHL disease.
Authors	G Siemeister, K Weindel, K Mohrs, B Barleon, G Martiny-Baron, D Marmé
Journal	Cancer research (Cancer Res) Vol. 56 Issue 10 Pg. 2299-301 (May 15 1996) ISSN: 0008-5472 [Print] United States
PMID	8625303 (Publication Type: Journal Article)
Chemical References	Endothelial Growth Factors Lymphokines MAS1 protein, human Neoplasm Proteins Proteins Proto-Oncogene Mas Recombinant Fusion Proteins Tumor Suppressor Proteins Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors Fibroblast Growth Factor 2 Ubiquitin-Protein Ligases Von Hippel-Lindau Tumor Suppressor Protein Ligases VHL protein, human
Topics	Carcinoma, Renal Cell (metabolism, pathology) Endothelial Growth Factors (biosynthesis, genetics, physiology) Fibroblast Growth Factor 2 (biosynthesis, genetics) Gene Expression Regulation, Neoplastic (drug effects) Genes, Tumor Suppressor Genes, myc Humans Kidney Neoplasms (metabolism, pathology) Ligases Lymphokines (biosynthesis, genetics, physiology) Neoplasm Proteins (biosynthesis, genetics, physiology) Neovascularization, Pathologic (genetics) Phenotype Protein Biosynthesis Proteins (genetics, physiology) Proto-Oncogene Mas Recombinant Fusion Proteins (metabolism) Transfection Tumor Cells, Cultured Tumor Suppressor Proteins Ubiquitin-Protein Ligases Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors Von Hippel-Lindau Tumor Suppressor Protein von Hippel-Lindau Disease (genetics)

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