Norris M D, Bordow S B, Haber P S, Marshall G M, Kavallaris M, Madafiglio J, Cohn S L, Salwen H, Schmidt M L, Hipfner D R, Cole S P, Deeley R G, Haber M
Children's Leukaemia and Cancer Research Centre, Sydney Children's Hospital, Randwick, N.S.W., Australia.
Eur J Cancer. 1997 Oct;33(12):1911-6. doi: 10.1016/s0959-8049(97)00284-0.
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.
我们最近发现，多药耐药相关蛋白（MRP）基因的表达是儿童神经母细胞瘤的一个有力预后指标，并提出MYCN癌基因可能调节MRP基因的表达。为了验证这一假设，我们研究了神经母细胞瘤肿瘤组织和细胞系中MYCN与MRP基因表达之间的关系。在60例未经治疗的原发性肿瘤中，无论有无MYCN基因扩增，MYCN和MRP基因表达均高度相关（有扩增时P = 0.01，无扩增时P < 0.0001）。与MRP一样，在整个研究人群以及无MYCN基因扩增的大龄儿童中，MYCN基因高表达均与生存率降低显著相关（相对风险分别为13.33和19.61）。通过在体外将MYCN反义RNA构建体导入人神经母细胞瘤细胞来抑制MYCN，经RNA-PCR和蛋白质免疫印迹分析确定，这导致了MRP基因表达下降。这些数据表明MYCN通过调节MRP基因表达影响神经母细胞瘤的预后。
