p53 does not repress hypoxia-induced transcription of the vascular endothelial growth factor gene.
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.
Agani
F
F
Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Kirsch
D G
DG
Friedman
S L
SL
Kastan
M B
MB
Semenza
G L
GL
D006528:Carcinoma, Hepatocellular; D015687:Cell Hypoxia; D002999:Clone Cells; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D017930:Genes, Reporter; D006801:Humans; D008113:Liver Neoplasms; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors