N-myc down-regulates activin A.
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.
Abteilung Hämatologie, Onkologie und Endokrinologie, Universitäts-Kinderklinik Essen, Hufelandstrasse 55, Essen, 45122, Germany.
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Breit
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Rössler
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Fotsis
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Schweigerer
D028341:Activins; D000595:Amino Acid Sequence; D002460:Cell Line; D002999:Clone Cells; D017077:Culture Media, Conditioned / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D005784:Gene Amplification; D017930:Genes, Reporter; D006801:Humans; D007265:Inhibins / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D029584:Prostatic Secretory Proteins; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D012175:Retinoblastoma / Q000378:metabolism* / Q000473:pathology; D020539:Sequence Analysis, Protein; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D017077:Culture Media, Conditioned; D010455:Peptides; D029584:Prostatic Secretory Proteins; D016271:Proto-Oncogene Proteins c-myc; D016212:Transforming Growth Factor beta; C043076:beta-microseminoprotein; C094377:inhibin-alpha subunit; D028341:Activins; D007265:Inhibins