N-myc disrupts protein kinase C-mediated signal transduction in neuroblastoma.
In neuroblastoma, amplification of the N-myc gene is closely correlated with increased metastatic ability. The mechanism by which N-myc acts to increase neuroblastoma malignancy is poorly understood as yet. It is shown here that transfection of N-myc in a neuroblastoma cell line causes suppression of one isoform of protein kinase C, named delta, and induction of an unusual type of protein kinase C, named zeta. N-myc-transfected neuroblastoma cells were found to be blocked in the activation of both c-fos mRNA and the NF-kappa B transcription factor by phorbol ester. Introduction of a protein kinase C expression vector in N-myc transfected neuroblastoma cells restored inducibility of both c-fos and NF-kappa B by phorbol ester. These observations indicate that changes in protein kinase C gene expression significantly alter the response of N-myc-amplified neuroblastomas to a variety of external signals.
Bernards
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Division of Molecular Genetics, Harvard Medical School, Charlestown, MA 02129.
D003600:Cytosol / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016328:NF-kappa B / Q000235:genetics; D009447:Neuroblastoma / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000096:biosynthesis / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate