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.
Lucarelli
E
E
Cellular & Molecular Biology Section, National Cancer Institute, National Institutes of Health, Rockville Pike, Maryland 20892, USA.
Kaplan
D
D
Thiele
C J
CJ
D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002455:Cell Division; D006801:Humans; D009414:Nerve Growth Factors / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000187:drug effects* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects* / Q000235:genetics; D020917:Receptor, trkA; D020813:Receptor, trkB; D017475:Receptors, Nerve Growth Factor / Q000187:drug effects* / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; D020813:Receptor, trkB