N-myc down-regulates activin A

N-myc oncogene amplification is frequent in human neuroblastoma and predict s poor prognosis, but the molecular consequences have remained obscure. We report here that enhanced N-myc expression correlates with low or undetecta ble expression of activin A, but not other closely related members of the t ransforming growth factor-beta superfamily, N-myc interacts with the activi n A promoter, eventually inducing down-regulation of activin A mRNA and pro tein. This study demonstrates for the first time N-myc-induced down-regulat ion of a gene implicated in signal transduction. Down-regulation of activin A could deprive neuroblastomas from a signal with growth-inhibitory activi ties toward the tumor and its stroma and thereby permit neuroblastoma progr ession. (C) 2000 Academic Press.