Wild-type p53 and v-Src exert opposing influences on human vascular endothelial growth factor gene expression.
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.
Beth Israel Hospital, Boston, Massachusetts 02215, USA.
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Mukhopadhyay
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Tsiokas
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Sukhatme
D016228:Endothelial Growth Factors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D016391:Genes, src; D006801:Humans; D008222:Lymphokines / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000235:genetics*; D015688:Oncogene Protein pp60(v-src) / Q000502:physiology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D015688:Oncogene Protein pp60(v-src)