Wild-type p53 and v-Src exert opposing influences on human vascular endothelial growth factor gene expression

• 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
• ISSN: 0008-5472; 1538-7445

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.