Bordow S B, Haber M, Madafiglio J, Cheung B, Marshall G M, Norris M D
Children's Leukaemia and Cancer Research Centre, Prince of Wales Children's Hospital, Randwick, Sydney, New South Wales, Australia.
Cancer Res. 1994 Oct 1;54(19):5036-40.
The MRP gene (Cole et al., Science (Washington DC), 258: 1650-1654, 1992) encodes a membrane-bound glycoprotein the expression of which correlates with non-P-glycoprotein-mediated multidrug resistance in a variety of cultured human cell lines. Using an RNA-polymerase chain reaction assay, expression of this gene was examined in the highly chemoresistant pediatric malignancy, neuroblastoma. MRP expression was observed in 5 human neuroblastoma cell lines and in all 25 primary neuroblastoma tumors of stage I through IVS. Tumors with amplification of the N-myc oncogene were found to have significantly higher MRP expression that those with no amplification (P = 0.0016). Expression of the MRP gene in the tumor specimens was highly correlated with expression of the N-myc gene (P = 0.0009), while expression of the MDR1 gene, encoding P-glycoprotein, was not related to expression of either the N-myc or MRP genes. Decreased expression of the N-myc oncogene in neuroblastoma cell lines SH-SY5Y and BE(2)-C, following treatment with retinoic acid, was paralleled by down-regulation of MRP gene expression, contrasting with increased expression of the MDR1 gene. Expression of the MRP gene is thus common in both primary neuroblastoma tumors and cultured cell lines, and correlates with amplification and overexpression of the N-myc oncogene, which is central to the malignant phenotype of this disease.
MRP基因（Cole等人，《科学》（华盛顿特区），258: 1650 - 1654，1992）编码一种膜结合糖蛋白，其表达与多种培养的人类细胞系中由非P - 糖蛋白介导的多药耐药性相关。使用RNA聚合酶链反应分析，在高度化疗耐药的儿童恶性肿瘤神经母细胞瘤中检测了该基因的表达。在5个人类神经母细胞瘤细胞系以及所有25例I期至IVS期的原发性神经母细胞瘤肿瘤中均观察到MRP表达。发现N - myc癌基因扩增的肿瘤其MRP表达显著高于无扩增的肿瘤（P = 0.0016）。肿瘤标本中MRP基因的表达与N - myc基因的表达高度相关（P = 0.0009），而编码P - 糖蛋白的MDR1基因的表达与N - myc或MRP基因的表达均无关。用视黄酸处理后，神经母细胞瘤细胞系SH - SY5Y和BE(2) - C中N - myc癌基因表达降低，同时MRP基因表达下调，这与MDR1基因表达增加形成对比。因此，MRP基因的表达在原发性神经母细胞瘤肿瘤和培养的细胞系中都很常见，并且与N - myc癌基因的扩增和过表达相关，而N - myc癌基因是该疾病恶性表型的核心。
