THE IMMEDIATE-EARLY GENE-PRODUCT MAD-3 EDG-3/I-KAPPA-B-ALPHA IS AN ENDOGENOUS MODULATOR OF FIBROBLAST GROWTH-FACTOR-I (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 o f the immediate-early gene, edg-3, which is identical to the I kappa B alpha/MAD-3 gene. We employed phosphothioate oligonucleotides (PTO) d irected against the translation initiation site of I kappa B alpha to inhibit its expression. The antisense I kappa B alpha PTO-treated cell s exhibited an exaggerated growth response to fibroblast growth factor -1 (FGF-1). In contrast, IL-1-induced growth arrest response was not m odulated. These data suggest that the early response gene I kappa B al pha is an endogenous regulator of endothelial cell growth in vitro. (C ) 1997 Federation of European Biochemical Societies.