EFFECT OF RETINOIC ACID ON P21(RAS) AND REGULATORS OF ITS ACTIVITY IN NEUROBLASTOMA

p21(ras) is a membrane-associated guanine nucleotide-binding protein with intrinsic GTPase activity. This protein is important in the regulation of cell growth and differentiation in a number of different cell types. Therefore, the aim of the present study was to examine the role of p21(ras) and regulators of its activity in the differentiation of neuroblastoma cells induced by retinoic acid (RA). Phosphorylation of p21(ras) is regulated by the GTPase activity of type I GAP(120) and neurofibromin. RA-induced differentiation of the two neuroblastoma cell lines SK-N-SH and IMR-32 was closely related to growth inhibition. Differentiation induced by RA resulted in an increase in both type I GAP(120) and neurofibromin mRNAs. This increase was accompanied by a decrease in the activation of p21(ras). These results suggest that, in neuroblastoma, activation of p21(ras) is not associated with RA-induced differentiation. However, the GTPase activating proteins type I GAP(120) and neurofibromin may have effector functions in RA-induced differentiation of neuroblastoma.