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 lines are responsive to the differentiation agent retinoic acid, which induces its effects by altering transcription rates of specific target genes. We identified autotaxin (ATX), which encodes an autocrine tumor motility-stimulating factor, as a gene whose expression is significantly induced by retinoic acid in neuroblastoma cells. ATX induction was specific for neuroblastoma cell lines that contain N-myc amplification, a cytogenetic feature commonly associated with aggressive neuroblastomas. Although ATX expression was associated with amplification of the N-myc locus, N-myc itself was neither sufficient nor required for ATX expression, suggesting that a coamplified gene is responsible. ATX induction by retinoic acid was due to increased transcription and required new protein synthesis.