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 th...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1995-12, Vol.55 (24), p.6161-6165
Main Authors: DEBABRATA MUKHOPADHYAY, TSIOKAS, L, SUKHATME, V. P
Format: Article
Language:English
Subjects:
Biological and medical sciences
Endothelial Growth Factors - genetics
Gene Expression Regulation, Neoplastic
Genes, p53
Genes, src
Humans
Lymphokines - genetics
Medical sciences
Multiple tumors. Solid tumors. Tumors in childhood (general aspects)
Neovascularization, Pathologic - genetics
Oncogene Protein pp60(v-src) - physiology
Promoter Regions, Genetic
RNA, Messenger - genetics
Transfection
Tumor Cells, Cultured
Tumor Suppressor Protein p53 - physiology
Tumors
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
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Summary: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.
ISSN:0008-5472
1538-7445