Wild-type p53 and v-Src exert opposing influences on human vascular endothelial growth factor gene expression.
Wild-type p53 and v-Src exert opposing influences on human vascular endothelial growth factor gene expression.
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发表时间：
1995-12
期刊：
影响因子：
11.2
通讯作者：
D. Mukhopadhyay;L. Tsiokas;V. Sukhatme
中科院分区：
文献类型：
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作者：
D. Mukhopadhyay;L. Tsiokas;V. Sukhatme
血管生成，即新毛细血管的发育，受到正调控通路和负调控通路的平衡的严格控制。血管内皮生长因子/血管通透性因子（VEGF/VPF）是一种新发现的血管生成因子，它能特异性地与内皮细胞结合并促进内皮细胞的增殖。在这里，我们研究了p53，肿瘤抑制基因，和v-Src，一个癌基因对VEGF的调节作用。野生型p53以剂量依赖性方式下调内源性VEGF mRNA水平以及VEGF启动子活性，而突变形式的p53没有影响。已知v-Src的过表达上调VEGF表达，以剂量依赖性方式激活VEGF启动子-荧光素酶构建体。此外，v-Src，在wt-p53的存在下，不能激活VEGF启动子的转录。总的来说，这些数据表明野生型p53可能在抑制血管生成中发挥作用。
Angiogenesis, the development of new capillaries, is tightly controlled by the balance of positive and negative regulatory pathways. A newly described angiogenic factor, vascular endothelial growth factor/vascular permeability factor (VEGF/VPF), binds exclusively to endothelial cells and promotes their proliferation. Here we have studied the role of p53, a tumor suppressor, and v-Src, an oncogene on VEGF regulation. Wild-type p53 down-regulated endogenous VEGF mRNA level, as well as VEGF promoter activity, in a dose-dependent manner, whereas mutant forms of p53 had no effect. Overexpression of v-Src, known to up-regulate VEGF expression, activated a VEGF promoter-luciferase construct in a dose-dependent manner. Moreover, v-Src, in the presence of wt-p53, was unable to activate transcription of the VEGF promoter. Collectively, these data suggest that wild-type p53 may play a role in suppressing angiogenesis.