Abstract
Hypoxia-induced neovascularization mediated by vascular endothelial growth factor (VEGF) contributes to tumor progression. Based on its effects when overexpressed in transient transfection assays, p53 has been proposed to repress VEGF transcription. To investigate this hypothesis, we have analyzed endogenous VEGF mRNA levels in Hep3B cells stably expressing an inducible p53-estrogen receptor fusion protein and in irradiated RKO cells expressing endogenous wild-type p53. In both cell lines, VEGF mRNA levels increased in response to hypoxia, either in the presence or absence of functional p53. Our data provide no evidence for a causal relationship between the loss of p53 activity and increased VEGF expression that is observed during tumor progression. Studies that attribute repressor functions to p53 based on analysis of cells transiently overexpressing this protein should be interpreted cautiously.
Footnotes
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↵1 Supported in part by a Fulbright Senior Scholar Award (to S. L. F.), by grants from the American Heart Association National Center (to G. L. S.), and by NIH Grants R01-DK39869 and R01-HL55338 (to G. L. S.), R01-ES05777 and R01-CA61949 (to M. B. K.), T32-GM07309 (to D. G. K.), and R01-DK37340 (to S. L. F.). G. L. S. is an Established Investigator of the American Heart Association, and M. B. K. is the Steven Birnbaum Scholar of the Leukemia Society of America.
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↵2 To whom requests for reprints should be addressed, at Johns Hopkins Hospital, CMSC-1004, 600 North Wolfe Street, Baltimore, MD 21287-3914. Phone: (410) 955-1619; Fax: (410) 955-0484; E-mail: gsemenza@gwgatel.jhmi.jhu.edu.
- Received July 14, 1997.
- Accepted August 29, 1997.
- ©1997 American Association for Cancer Research.
Volume 57, Issue 20
