Evidence that the MYCN oncogene regulates MRP gene expression in neuroblastoma

Abstract We have recently shown that expression of the multidrug resistance-associated protein ( MRP ) gene is a powerful prognostic indicator in childhood neuroblastoma and have suggested that the MYC N oncogene may regulate MRP gene expression. To address this hypothesis, we have examined the relationship between MYC N and MRP gene expression in neuroblastoma tumours and cell lines. MYC N and MRP gene expression were highly correlated in 60 primary untreated tumours both with ( P  = 0.01) and without MYC N gene amplification ( P MRP , high MYC N gene expression was significantly associated with reduced survival, both in the overall study population and in older children without MYC N gene amplification (relative hazards = 13.33 and 19.61, respectively). Inhibition of MYC N, through the introduction of MYC N antisense RNA constructs into human neuroblastoma cells in vitro , resulted in decreased MRP gene expression, determined both by RNA–PCR and Western analysis. The data are consistent with MYC N influencing neuroblastoma outcome by regulating MRP gene expression.