Constitutive N-myc gene expression inhibits trkA mediated neuronal differentiation.
The effect of constitutively expressed N-myc gene on nerve growth factor (NGF) induced neuronal differentiation was investigated. B104, a rat central nervous system-derived cell line and its N-myc gene expressing derivative lines (C6, C7) (Bernards et al., 1986), were stably transfected with the trkA proto-oncogene and independent clones for each cell line were analysed. NGF induced phosphorylation of the trkA receptor, activated a cascade of cellular intermediaries such as phospholipase C gamma 1 and ERK proteins, and stimulated c-fos gene transcription in all trkA-expressing clones. NGF-mediated neuronal differentiation was observed solely in trkA-expressing B104-derived clones and was characterized by reduced cell growth, activation of NGF-regulated genes, and downregulation of the endogenous low-affinity NGF receptor gene (gp75NGFR). No such phenotypical changes occurred in trkA-expressing C6 or C7-derived clones following NGF treatment. These results are consistent with the hypothesis that constitutive expression of N-myc inhibits exit from cell cycle and blocks neuronal cell differentiation.
Bogenmann
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Division of Hematology-Oncology, Childrens Hospital Los Angeles Research Institute, California 90027, USA.
Torres
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Matsushima
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D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos / Q000502:physiology; D016259:Genes, myc / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology*; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*
D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA