Activation of trk-A but not trk-B signal transduction pathway inhibits growth of neuroblastoma cells.

In neuroblastoma tumours, the expression of high levels of trk-A mRNA, which encodes the high-affinity nerve growth factor (NGF) receptor, is associated with good prognosis. Constitutive expression of brain-derived neurotrophic factor (BDNF) and variable expression of its receptor trk-B are frequently detected in tumours from patients with a poor prognosis. To evaluate the biological consequences of activation of the trk-A or trk-B signal transduction pathways in neuroblastoma cells, the trk-A or trk-B gene was transfected into the trk negative 15N neuroblastoma cell line. Clones expressing trk-A or trk-B were treated with specific ligands and evaluated for growth and differentiation. Both ligands induced neurite extension. Treatment of the 15N-trk-A clones with NGF inhibited proliferation (80-90% decrease), while treatment of the 15N-trk-B clone with BDNF had no effect (< 10% decrease). NGF-induced growth inhibition was concentration dependent. Such studies indicate that differential trk expression may affect the biology of neuroblastoma tumours and contribute to differences in the clinical course of patients.