P53 DOES NOT REPRESS HYPOXIA-INDUCED TRANSCRIPTION OF THE VASCULAR ENDOTHELIAL GROWTH-FACTOR GENE

Hypoxia-induced neovascularization mediated by vascular endothelial gr owth factor (VEGF) contributes to tumor progression, Based on its effe cts 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 e xpressing an inducible p53-estrogen receptor fusion protein and in irr adiated RKO cells expressing endogenous wild-type p53, In both cell li nes, VEGF mRNA levels increased in response to hypoxia, either in the presence or absence of functional p53. Our data provide no evidence fo r a causal relationship between the loss of p53 activity and increased VEGF expression that is observed during tumor progression, Studies th at attribute repressor functions to p53 based on analysis of cells tra nsiently overexpressing this protein should be interpreted cautiously.