Sa. Burchill et al., EFFECT OF RETINOIC ACID ON P21(RAS) AND REGULATORS OF ITS ACTIVITY INNEUROBLASTOMA, European journal of cancer, 31A(4), 1995, pp. 476-481
p21(ras) is a membrane-associated guanine nucleotide-binding protein w
ith intrinsic GTPase activity. This protein is important in the regula
tion 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 ne
urofibromin. RA-induced differentiation of the two neuroblastoma cell
lines SK-N-SH and IMR-32 was closely related to growth inhibition. Dif
ferentiation induced by RA resulted in an increase in both type I GAP(
120) and neurofibromin mRNAs. This increase was accompanied by a decre
ase in the activation of p21(ras). These results suggest that, in neur
oblastoma, activation of p21(ras) is not associated with RA-induced di
fferentiation. However, the GTPase activating proteins type I GAP(120)
and neurofibromin may have effector functions in RA-induced different
iation of neuroblastoma.