Effect of retinoic acid on p21ras and regulators of its activity in neuroblastoma

Abstract 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.