Sa. Burchill et al., CHANGING EXPRESSION OF GTPASE-ACTIVATING PROTEINS WITH DIFFERENTIATION IN NEUROBLASTOMA, Journal of the neurological sciences, 126(2), 1994, pp. 126-132
p21(ras) is a membrane-associated guanine nucleotide-binding protein w
ith intrinsic GTPase activity. Like other guanine nucleotide-binding p
roteins p21(ras) is active when GTP bound and inactive when GDP bound.
Phosphorylation of p21(ras) is regulated by the GTPase activity of ty
pe I GAP(120) and NF1-GRD. In this study we have identified type I GAP
(120) and two NF1-GRD mRNAs in three neuroblastoma cell lines, IMR-32,
SK-N-SH and SK-N-MC. NF1-GRD mRNA was expressed in all cell lines at
a similar level but type I GAP(120) mRNA was more abundant in the IMR-
32 cell line. Retinoic acid induced differentiation of all three cell
lines, this effect was most marked in the SK-N-SH line. This different
iation was accompanied by an increase in both type I GAP(120) and NF1-
GRD mRNAs. Retinoic acid induced differentiation had no effect on the
ratio of type I to type II NF1-GRD mRNA. In seven patient tumour sampl
es examined type I GAP(120) and NF1-GRD were coexpressed, type I GAP(1
20) at a higher level than NF1-GRD in all tumour stages. Type I was th
e predominant NF1-GRD mRNA. The expression of type I GAP(120) was simi
lar in all tumour stages but the total level of NF1-GRD was higher in
stage 2 and 3 tumours than in stage 4 tumours. In summary, these resul
ts suggest increased type I GAP(120) and NF1-GRD mRNA are associated w
ith differentiation in neuroblastoma cells.