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 inhibitor of tyrosine kinase C, on spontaneous and basic FGF-induced proliferation of the epithelial cell lines A549 and HELA as well as the neuroblastoma cell line SY5Y using a fully automated colorimetric assay for determinations of cell numbers. HOE-BAY suppressed spontaneous proliferation 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 suggests an involvement of a tyrosine kinase C activity in the transduction of the FGF signal both in the epithelial and neuroblastoma lines. Since the action of FGF on non-transformed neuronal cells is accompanied by a down-regulation of kinase C, and kinase C activation blocks the FGF effects, our data indicate that differentiative and mitogenic effects of FGF on neuronal cells may employ different transduction mechanisms.