Insulin-like growth factor-II expression is down-regulated in TrkA-transfected SK-N-AS neuroblastoma cells

Expression level of trkA tyrosine kinase receptor for nerve growth factor i s a major prognostic determinant of neuroblastoma, suggesting that defectiv e trkA-mediated signaling is responsible for the tumorigenesis of this chil dhood malignancy. We investigated the biologic effect of trkA, with special reference to its effect on insulin-like growth factor-it (IGF-II) expressi on, in SK-N-AS human neuroblastoma cells transfected with human trkA cDNA. Nerve growth factor treatment of trkA-transfected cells promoted growth and changed the morphologic phenotype into a substrate-adherent, flatter pheno type (S-type), and down-regulated the mRNA expression of IGF-II. The effect s on both growth and the morphologic differentiation of SK-N-AS cells diffe red significantly from those of previous studies, and implied that trkA eff ects can be diverse, depending on the phenotype of the individual neuroblas toma cells. Immunohistochemical screening of trkA and IGF-II expression in adrenal neuroblastomas (n = 25) also favored the nonoverlapping pattern of trkA and IGF-II expression (p < 0.05). Because IGF-II is believed to play a significant role in the tumorigenesis of neuroblastoma, the inverse relati onship between trkA and IGF-H strongly suggests that a low level of trkA ca n be a feature of the pathogenetic mechanism of IGF-II expressing adrenal n euroblastomas.