HYPOXIA-INDUCED TRANSCRIPTION OF THE VASCULAR ENDOTHELIAL GROWTH-FACTOR GENE IS INDEPENDENT OF FUNCTIONAL AP-1 TRANSCRIPTION FACTOR

In this study, we investigated the functional role of the transcriptio n factor AP-1 in hypoxia-induced expression of the vascular endothelia l growth factor (VEGF) by using dexamethasone as an inhibitor of AP-1 activity. Phorbol ester and platelet-derived growth factor (PDGF) caus e an increase in VEGF mRNA expression, which is strongly suppressed in the presence of dexamethasone, whereas hypoxia-induced VEGF expressio n is not inhibited by dexamethasone. Studies using a VEGF promoter luc iferase construct show that the phorbol ester and PDGF-induced VEGF ex pression is mediated at least in part by transcriptional activation of the VEGF promoter, whereas no transcriptional activation is seen unde r hypoxic conditions. In contrast, hypoxia leads to an increase in VEG F mRNA stability, as confirmed by experiments using actinomycin D as a n inhibitor of transcription. These results indicate that hypoxia-indu ced VEGF expression is independent of AP-1 mediated transcription. (C) 1995 Academic Press, Inc.