title: TrkA signal transduction pathways in neuroblastoma.
abstract: BACKGROUND
  Favorable neuroblastomas frequently express high levels of the TrkA receptor, and these tumors have a propensity to either differentiate or regress, but the mechanisms responsible for these two fates are unclear.
  
  
  METHODS
  To study TrkA signal transduction in neuroblastoma (nb), we stably expressed wild-type TrkA and five TrkA mutants in the human nb cell line SH-SY5Y. Resulting single cell clones were characterized by TrkA mRNA and protein expression and by autophosphorylation of the receptor.
  
  
  RESULTS
  Introduction of TrkA restored nerve growth factor (NGF) responsiveness of SH-SY5Y cells, demonstrated by morphological differentiation and induction of immediate-early genes. TrkA overexpression leads to growth inhibition in the absence of NGF, whereas NGF treatment results in increased proliferation.
  
  
  CONCLUSIONS
  Analysis of downstream signaling elements in mutated TrkA receptors indicates that NGF-induced differentiation is dependent on TrkA kinase activity, but several redundant pathways seem to be used farther downstream. This suggests differences from TrkA pathways identified in PC12 cells.
authors.affiliation: Division of Oncology, Children's Hospital of Philadelphia, Pennsylvania 19104, USA.
authors.forename: A
authors.initials: A
authors.lastname: Eggert
authors.forename: N
authors.initials: N
authors.lastname: Ikegaki
authors.forename: X G
authors.initials: XG
authors.lastname: Liu
authors.forename: T T
authors.initials: TT
authors.lastname: Chou
authors.forename: G M
authors.initials: GM
authors.lastname: Brodeur
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D001665:Binding Sites; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D009363:Neoplasm Proteins / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020932:Nerve Growth Factor / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D051966:Phospholipase C gamma; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D020917:Receptor, trkA / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D003470:Culture Media; D016895:Culture Media, Serum-Free; D007527:Isoenzymes; D009363:Neoplasm Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D010738:Type C Phospholipases; D051966:Phospholipase C gamma