The immediate-early gene product MAD-3/EDG-3/IkappaB alpha is an endogenous modulator of fibroblast growth factor-1 (FGF-1) dependent human endothelial cell growth.
The tumor promoter phorbol 12-myristic 13-acetate inhibits the growth of human endothelial cells and induces the formation of capillary-like, tubular structures. We report the novel growth regulatory function of the immediate-early gene, edg-3, which is identical to the IkappaB alpha/MAD-3 gene. We employed phosphothioate oligonucleotides (PTO) directed against the translation initiation site of IkappaB alpha to inhibit its expression. The antisense IkappaB alpha PTO-treated cells exhibited an exaggerated growth response to fibroblast growth factor-1 (FGF-1). In contrast, IL-1-induced growth arrest response was not modulated. These data suggest that the early response gene IkappaB alpha is an endogenous regulator of endothelial cell growth in vitro.
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Department of Physiology, University of Connecticut School of Medicine, Farmington 06030, USA. hla@sun.uchc.edu
Zimrin
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Evans
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Ballas
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Maciag
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D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D017781:Genes, Immediate-Early / Q000187:drug effects; D006801:Humans; D020672:I-kappa B Proteins; D017874:Immediate-Early Proteins / Q000096:biosynthesis*; D000072000:NF-KappaB Inhibitor alpha; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D049312:Receptors, Lysophospholipid; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013873:Thionucleotides; D014471:Umbilical Veins
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D017874:Immediate-Early Proteins; C000606204:NFKBIA protein, human; D016376:Oligonucleotides, Antisense; D049312:Receptors, Lysophospholipid; D013873:Thionucleotides; D016220:Fibroblast Growth Factor 1; D000072000:NF-KappaB Inhibitor alpha; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate