Up-regulation of insulin-like growth factor-II expression is a feature of trkA but not trkB activation in SH-SY5Y neuroblastoma cells

The types of neurotrophin receptors that are expressed in neuroblastomas ha ve different prognostic implications; trkA is a marker of good prognosis, w hereas trkB expression is associated with poor prognosis. This suggests tha t either the signaling that is mediated via these receptors modulates the b iological features of neuroblastoma cells differently, or that distinct lin eages of sympathoadrenal precursors have been transformed. In this report, we evaluate the biological effects after activation of trkA or trkB by thei r major ligands in SH-SY5Y human neuroblastoma cells. Both trkA and trkB in duce differentiation, inhibit growth, and promote the survival of cells und er conditions of nutrient deprivation. However, the up-regulation of insuli n-like growth factor-II (IGF-II) expression is a predominant feature of trk A. activation by nerve growth factor (NGF). The growth inhibition induced b y blocking the insulin-like growth factor-I receptor suggests that IGF-II i s a component of the effector mechanism of trkA activation by NGF in trkA-t ransfected cells. Although trkA and trkB expression is associated with diff erent prognoses in neuroblastoma, our study indicates that the effects medi ated by these receptors in vivo may be quite similar for certain subsets of neuroblastomas.