title: 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 MYCN oncogene may regulate 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 correlated in 60 primary untreated tumours both with (P = 0.01) and without MYCN gene amplification (P < 0.0001). Like MRP, high MYCN gene expression was significantly associated with reduced survival, both in the overall study population and in older children without MYCN gene amplification (relative hazards = 13.33 and 19.61, respectively). Inhibition of MYCN, through the introduction of MYCN 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 MYCN influencing neuroblastoma outcome by regulating MRP gene expression.
authors.affiliation: Children's Leukaemia and Cancer Research Centre, Sydney Children's Hospital, Randwick, N.S.W., Australia.
authors.forename: M D
authors.initials: MD
authors.lastname: Norris
authors.forename: S B
authors.initials: SB
authors.lastname: Bordow
authors.forename: P S
authors.initials: PS
authors.lastname: Haber
authors.forename: G M
authors.initials: GM
authors.lastname: Marshall
authors.forename: M
authors.initials: M
authors.lastname: Kavallaris
authors.forename: J
authors.initials: J
authors.lastname: Madafiglio
authors.forename: S L
authors.initials: SL
authors.lastname: Cohn
authors.forename: H
authors.initials: H
authors.lastname: Salwen
authors.forename: M L
authors.initials: ML
authors.lastname: Schmidt
authors.forename: D R
authors.initials: DR
authors.lastname: Hipfner
authors.forename: S P
authors.initials: SP
authors.lastname: Cole
authors.forename: R G
authors.initials: RG
authors.lastname: Deeley
authors.forename: M
authors.initials: M
authors.lastname: Haber
mesh_terms: D000367:Age Factors; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D005500:Follow-Up Studies; D005784:Gene Amplification / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D019450:Genes, MDR / Q000235:genetics*; D016259:Genes, myc / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007223:Infant; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D016016:Proportional Hazards Models; D016372:RNA, Antisense / Q000494:pharmacology; D012044:Regression Analysis; D016019:Survival Analysis; D014407:Tumor Cells, Cultured
chemical_list: D016372:RNA, Antisense