BASIC FGF AND IGF-I PROMOTE DIFFERENTIATION OF HUMAN SH-SY5Y NEUROBLASTOMA-CELLS IN CULTURE

Phorbolester-triggered differentiation of SH-SY5Y neuroblastoma cells requires serum and a prolonged activation of protein kinase C (PKC). U nder serum-free conditions development of a mature phenotype requires phorbolester in combination with a member of either the insulin-like g rowth factor (IGF) or the platelet-derived growth factor family. Here we report that basic and acidic fibroblast growth factor (FGF) and epi dermal growth factor, but not nerve growth factor, synergistically pot entiate phorbolester-induced differentiation. Alone these factors indu ced a mitogenic response which varied in magnitude, with basic FGF and IGF-I being the two most potent mitogens. However, a combination of b asic FGF and IGF-I induced differentiation as judged by morphology and the increase in growth associated protein (GAP-43) and neuropeptide t yrosine mRNA levels. In contrast to the phenotype obtained in the pres ence of phorbolester, bFGF and IGF-I-treated SH-SY5Y cells retained th eir capacity to proliferate. Finally, in these cells, the phosphorylat ion of the endogenous PKC substrate, myristoylated alanine-rich C-kina se substrate (MARCKS), was slightly increased during several days, sug gesting an involvement of PKC in the bFGF and IGF-I-induced differenti ation.