HOE-BAY 946 HAS DISTINCT EFFECTS ON SPONTANEOUS AND FGF INDUCED PROLIFERATION OF EPITHELIAL AND NEUROBLASTOMA CELL-LINES

We have studied in vitro the effects of HOE-BAY 946, a specific inhibi tor of tyrosine kinase C, on spontaneous and basic FGF-induced prolife ration of the epithelial cell lines A549 and HELA as well as the neuro blastoma cell line SY5Y using a fully automated colorimetric assay for determinations of cell numbers. HOE-BAY suppressed spontaneous prolif eration of the epithelial lines, but not the neuroblastoma line, both in the presence and absence of serum. In contrast, the drug completely abolished the mitogenic effect of basic FGF on all cell lines. This s uggests an involvement of a tyrosine kinase C activity in the transduc tion of the FGF signal both in the epithelial and neuroblastoma lines. Since the action of FGF on non-transformed neuronal cells is accompan ied by a down-regulation of kinase C, and kinase C activation blocks t he FGF effects, our data indicate that differentiative and mitogenic e ffects of FGF on neuronal cells may employ different transduction mech anisms.