|Differences in early and late responses between neurotrophin-stimulated trkA- and trkC-transfected SH-SY5Y neuroblastoma cells.|
|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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|Type: Journal Article; Research Support, Non-U.S. Gov't|
|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|
|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|
|Languages: eng Pagination: 39-50 Citation Subset: IM|
|Department of Laboratory Medicine, Lund University, University Hospital MAS, Malmö, Sweden.|
|APA/MLA Format Download EndNote Download BibTex|
Dose-Response Relationship, Drug
Electrophoresis, Polyacrylamide Gel
Fibroblast Growth Factors / metabolism
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
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
Synaptophysin / biosynthesis, metabolism
Tumor Cells, Cultured
ras Proteins / metabolism
|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 220.127.116.11/Receptor, trkA; EC 18.104.22.168/Receptor, trkC; EC 22.214.171.124/AKT1 protein, human; EC 126.96.36.199/Protein-Serine-Threonine Kinases; EC 188.8.131.52/Proto-Oncogene Proteins c-akt; EC 184.108.40.206/Mitogen-Activated Protein Kinase 3; EC 220.127.116.11/Mitogen-Activated Protein Kinases; EC 18.104.22.168/ras Proteins|
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