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 transcription factor AP-1 in hypoxia-induced expression of the vascular endothelial growth factor (VEGF) by using dexamethasone as an inhibitor of AP-1 activity. Phorbol ester and platelet-derived growth factor (PDGF) cause an increase in VEGF mRNA expression, which is strongly suppressed in the presence of dexamethasone, whereas hypoxia-induced VEGF expression is not inhibited by dexamethasone. Studies using a VEGF promoter luciferase construct show that the phorbol ester and PDGF-induced VEGF expression is mediated at least in part by transcriptional activation of the VEGF promoter, whereas no transcriptional activation is seen under hypoxic conditions. In contrast, hypoxia leads to an increase in VEGF mRNA stability, as confirmed by experiments using actinomycin D as an inhibitor of transcription. These results indicate that hypoxia-induced VEGF expression is independent of AP-1 mediated transcription.
Finkenzeller
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G
Institute for Molecular Medicine, Tumor Biology Center, Freiburg, Germany.
Technau
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A
Marmé
D
D
D016475:3T3 Cells; D000818:Animals; D000077214:Becaplermin; D015152:Blotting, Northern; D015687:Cell Hypoxia; D003907:Dexamethasone / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D008156:Luciferases / Q000032:analysis / Q000096:biosynthesis; D008222:Lymphokines / Q000096:biosynthesis*; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000096:biosynthesis / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D011994:Recombinant Proteins; D018808:Transcription Factor AP-1; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000077214:Becaplermin; D003907:Dexamethasone; D008156:Luciferases; D013755:Tetradecanoylphorbol Acetate