Transfection of TRK-A into human neuroblastoma cells restores their ability to differentiate in response to nerve growth factor.
Human neuroblastoma cell lines frequently express the TRK-A proto-oncogene and bind nerve growth factor (NGF) but do not differentiate when exposed to NGF. Transient transfection of an exogenous TRK-A gene into SH-SY5Y and LA-N-5 neuroblastoma cells restored the ability of these tumor cells to differentiate with NGF. Stable TRK-A-transfected SH-SY5Y cell clones were isolated, and they responded to NGF by autophosphorylation of p140trk-A, c-fos induction, morphological differentiation, and increased expression of two neuronal marker genes, neuropeptide tyrosine and GAP-43. In phorbol ester-induced differentiated wild-type cells, TRK-A expression was increased with no change in NGF responsiveness. Thus, the restoration of the NGF-induced differentiation pathway by exogenous TRK-A presents a system of NGF-responsive human cultured cells and focuses attention on the trk-A protein and its function or malfunction in neuroblastoma.
Lavenius
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Department of Pathology, University of Uppsala, University Hospital, Sweden.
Gestblom
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C
Johansson
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I
Nånberg
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E
Påhlman
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S
D002454:Cell Differentiation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009447:Neuroblastoma / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D011519:Proto-Oncogenes; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D009414:Nerve Growth Factors; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D017475:Receptors, Nerve Growth Factor; D011993:Recombinant Fusion Proteins; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA