EVIDENCE THAT THE MYCN ONCOGENE REGULATES MRP GENE-EXPRESSION IN NEUROBLASTOMA

We have recently shown that expression of the multidrug resistance-ass ociated protein (MRP) gene is a powerful prognostic indicator in child hood neuroblastoma and have suggested that the MYCN oncogene may regul ate MRP gene expression. To address this hypothesis, we have examined the relationship between MYCN and MRP gene expression in neuroblastoma tumours and cell lines. MYCN and MRP gene expression were highly corr elated in 60 primary untreated tumours both with (P = 0.01) and withou t MYCN gene amplification (P < 0.0001). Like MRP, high MYCN gene expre ssion was significantly associated with reduced survival, both in the overall study population and in older children without MYCN gene ampli fication (relative hazards = 13.33 and 19.61, respectively). Inhibitio n of MYCN, through the introduction of MYCN antisense RNA constructs i nto human neuroblastoma cells in vitro, resulted in decreased MRP gene expression, determined both by RNA-PCR and Western analysis. The data are consistent with MYCN influencing neuroblastoma outcome by regulat ing MRP gene expression. (C) 1997 Elsevier Science Ltd.