Abstract
N-myc oncogene amplification is frequent in human neuroblastoma and predicts poor prognosis, but the molecular consequences have remained obscure. We report here that enhanced N-myc expression correlates with low or undetectable expression of activin A, but not other closely related members of the transforming growth factor-beta superfamily. N-myc interacts with the activin A promoter, eventually inducing down-regulation of activin A mRNA and protein. This study demonstrates for the first time N-myc-induced down-regulation of a gene implicated in signal transduction. Down-regulation of activin A could deprive neuroblastomas from a signal with growth-inhibitory activities toward the tumor and its stroma and thereby permit neuroblastoma progression.
Copyright 2000 Academic Press.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Activins
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Amino Acid Sequence
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Cell Line
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Clone Cells
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Culture Media, Conditioned / metabolism
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Down-Regulation / drug effects
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Down-Regulation / physiology*
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Gene Amplification
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Genes, Reporter
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Humans
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Inhibins / genetics
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Inhibins / metabolism*
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Kidney / cytology
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Kidney / metabolism*
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Molecular Sequence Data
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Neuroblastoma / metabolism*
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Neuroblastoma / pathology
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Peptides / metabolism
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Promoter Regions, Genetic / drug effects
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Prostatic Secretory Proteins*
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Proto-Oncogene Proteins c-myc / genetics
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Proto-Oncogene Proteins c-myc / metabolism*
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Proto-Oncogene Proteins c-myc / pharmacology
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Retinoblastoma / metabolism*
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Retinoblastoma / pathology
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Sequence Analysis, Protein
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Transcription, Genetic / drug effects
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Transfection
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Transforming Growth Factor beta / biosynthesis
Substances
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Culture Media, Conditioned
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Peptides
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Prostatic Secretory Proteins
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Proto-Oncogene Proteins c-myc
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Transforming Growth Factor beta
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beta-microseminoprotein
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inhibin-alpha subunit
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Activins
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Inhibins