Abstract
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, and 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.
Footnotes
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↵1 This work was supported in part by NIH Grant DK44921 (to V. P. S.).
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↵2 To whom requests for reprints should be addressed, at Beth Israel Hospital, 330 Brookline Avenue, Boston, MA 02215. Phone: (617) 667-2105; Fax: (617) 667-7843.
- Received July 11, 1995.
- Accepted October 11, 1995.
- ©1995 American Association for Cancer Research.
Volume 55, Issue 24
