Abstract
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.
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Cell Division / drug effects
-
Cells, Cultured
-
Cycloheximide / pharmacology
-
DNA-Binding Proteins / biosynthesis*
-
Endothelium, Vascular / cytology*
-
Endothelium, Vascular / drug effects
-
Endothelium, Vascular / metabolism*
-
Fibroblast Growth Factor 1 / pharmacology*
-
Genes, Immediate-Early / drug effects
-
Humans
-
I-kappa B Proteins*
-
Immediate-Early Proteins / biosynthesis*
-
NF-KappaB Inhibitor alpha
-
Oligonucleotides, Antisense / pharmacology
-
Polymerase Chain Reaction
-
Protein Biosynthesis
-
Receptors, Lysophospholipid
-
Tetradecanoylphorbol Acetate / pharmacology
-
Thionucleotides
-
Umbilical Veins
Substances
-
DNA-Binding Proteins
-
I-kappa B Proteins
-
Immediate-Early Proteins
-
NFKBIA protein, human
-
Oligonucleotides, Antisense
-
Receptors, Lysophospholipid
-
Thionucleotides
-
Fibroblast Growth Factor 1
-
NF-KappaB Inhibitor alpha
-
Cycloheximide
-
Tetradecanoylphorbol Acetate