Siemeister G, Weindel K, Mohrs K, Barleon B, Martiny-Baron G, Marmé D
Institute of Molecular Medicine, Tumor Biology Center, Freiburg, Germany.
Cancer Res. 1996 May 15;56(10):2299-301.
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.
在散发性肾细胞癌以及患冯·希佩尔-林道（VHL）综合征个体所发生的肿瘤中，已证实存在VHL肿瘤抑制基因的两个等位基因发生突变或缺失的情况。VHL病中形成的肿瘤具有血管丰富的表型，这让我们认为血管内皮生长因子（VEGF）是VHL病中肿瘤生长的介导因子。缺乏内源性野生型VHL或转染了无活性突变型VHL的人肾癌细胞，在mRNA和蛋白质水平上均表现出VEGF表达失调，而引入野生型VHL后这种失调得以恢复。通过中和VEGF，表达突变型VHL的细胞条件培养基对内皮细胞增殖的刺激作用几乎完全消除。相比之下，碱性成纤维细胞生长因子和c-myc原癌基因的表达不受VHL影响。我们的数据表明VEGF是VHL病中关键的肿瘤血管生成因子。
