G. Finkenzeller et al., HYPOXIA-INDUCED TRANSCRIPTION OF THE VASCULAR ENDOTHELIAL GROWTH-FACTOR GENE IS INDEPENDENT OF FUNCTIONAL AP-1 TRANSCRIPTION FACTOR, Biochemical and biophysical research communications, 208(1), 1995, pp. 432-439
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.