Retinoic acid-induced expression of autotaxin in N-myc-amplified neuroblastoma cells

Neuroblastoma, the most common extracranial solid tumor in children, arises from precursors of the sympathetic nervous system. Neuroblastoma cell line s are responsive to the differentiation agent retinoic acid, which induces its effects by altering transcription rates of specific target genes. We id entified autotaxin (ATX), which encodes an autocrine tumor motility-stimula ting factor, as a gene whose expression is significantly induced by retinoi c acid in neuroblastoma cells. ATX induction was specific for neuroblastoma cell lines that contain N-myc amplification, a cytogenetic feature commonl y associated with aggressive neuroblastomas. Although ATX expression was as sociated with amplification of the N-myc locus, N-myc itself was neither su fficient nor required for ATX expression, suggesting that a coamplified gen e is responsible. ATX induction by retinoic acid was due to increased trans cription and required new protein synthesis. (C) 2001 Wiley-Liss, inc.