Document Detail

Differences in early and late responses between neurotrophin-stimulated trkA- and trkC-transfected SH-SY5Y neuroblastoma cells.
MedLine Citation:
PMID:  11205744     Owner:  NLM     Status:  MEDLINE    
Despite their sympathetic neuroblast origin, highly malignant neuroblastoma tumors and derived cell lines have no or low expression of the neurotrophin receptor genes, trkA and trkC. Expression of exogenous trkA in neuroblastoma cells restores their ability to differentiate in response to nerve growth factor (NGF). Here we show that stable expression of trkC in SH-SY5Y neuroblastoma cells resulted in morphological and biochemical differentiation upon treatment with neurotrophin-3 (NT-3). To some extent, trkA- and trkC-transfected SH-SY5Y (SH-SY5Y/trkA and SH-SY5Y/trkC) cells resembled one another in terms of early signaling events and neuronal marker gene expression, but important differences were observed. Although induced Erk 1/2 and Akt/PKB phosphorylation was stronger in NT-3-stimulated SH-Y5Y/trkC cells, activation of the immediate-early genes tested was more prominent in NGF-treated SH-SY5Y/ trkA cells. In particular, c-fos was not induced in the SH-SY5Y/trkC cells. There were also phenotypic differences. The concentrations of norepinephrine, the major sympathetic neurotransmitter, and growth cone-located synaptophysin, a neurosecretory granule protein, were increased in NGF-treated SH-SY5Y/trkA but not in NT-3-treated SH-SY5Y/trkC cells. Our data suggest that NT-3/p145trkC and NGF/p140trkA signaling differ in some aspects in neuroblasoma cells, and that this may explain the phenotypic differences seen in the long-term neurotrophin-treated cells.
A Edsjö; B Hallberg; S Fagerström; C Larsson; H Axelson; S Påhlman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research     Volume:  12     ISSN:  1044-9523     ISO Abbreviation:  Cell Growth Differ.     Publication Date:  2001 Jan 
Date Detail:
Created Date:  2001-02-02     Completed Date:  2001-03-29     Revised Date:  2012-06-22    
Medline Journal Info:
Nlm Unique ID:  9100024     Medline TA:  Cell Growth Differ     Country:  United States    
Other Details:
Languages:  eng     Pagination:  39-50     Citation Subset:  IM    
Department of Laboratory Medicine, Lund University, University Hospital MAS, Malmö, Sweden.
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MeSH Terms
Blotting, Northern
Cell Differentiation
Dose-Response Relationship, Drug
Electrophoresis, Polyacrylamide Gel
Fibroblast Growth Factors / metabolism
Microscopy, Phase-Contrast
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases / metabolism
Nerve Growth Factor / metabolism,  pharmacology
Nerve Growth Factors / metabolism*
Neuroblastoma / metabolism*
Neurons / metabolism
Neurotrophin 3 / metabolism*
Norepinephrine / biosynthesis
Protein-Serine-Threonine Kinases*
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-akt
Proto-Oncogene Proteins c-fos / biosynthesis
RNA / metabolism
Receptor, trkA / genetics*,  metabolism
Receptor, trkC / genetics*,  metabolism
Signal Transduction
Synaptophysin / biosynthesis,  metabolism
Time Factors
Tumor Cells, Cultured
ras Proteins / metabolism
Reg. No./Substance:
0/Nerve Growth Factors; 0/Neurotrophin 3; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-fos; 0/Synaptophysin; 51-41-2/Norepinephrine; 62031-54-3/Fibroblast Growth Factors; 63231-63-0/RNA; 9061-61-4/Nerve Growth Factor; EC, trkA; EC, trkC; EC protein, human; EC Kinases; EC Proteins c-akt; EC Protein Kinase 3; EC Protein Kinases; EC Proteins

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