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Institute of Molecular Medicine, Tumor Biology Center, Breisacher Strasse 117, D-79106 Freiburg, Germany
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.
1 This work is dedicated to Professor Dr. Gerd Nagel on occasion of his 60th birthday.
2 To whom requests for reprints should be addressed. Phone: 49-761-206-1700; Fax: 49-761-206-1705.
Received 3/15/96. Accepted 4/ 9/96.
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