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首页> 外文期刊>British Journal of Cancer >High levels of the MDM2 oncogene in paediatric rhabdomyosarcoma cell lines may confer multidrug resistance
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High levels of the MDM2 oncogene in paediatric rhabdomyosarcoma cell lines may confer multidrug resistance

机译：小儿横纹肌肉瘤细胞系中高水平的MDM2癌基因可能赋予多药耐药性

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摘要

The MDM2 protein is known to be overexpressed in some sarcomas including rhabdomyosarcoma. However, the extent to which the MDM2 protein influences sensitivity to chemotherapeutic drugs is unclear. We have analysed this further using stable transfection of the mdm2 gene into 4 well-characterised human paediatric rhabdomyosarcoma cell lines. Transfection with the mdm2 gene resulted in increased levels of the MDM2 protein in all the cell lines. In 2 of the lines, SCMC and RD, the mdm2 gene caused between 2-fold and 61-fold increase in resistance to vincristine, etoposide and doxorubicin but not to cisplatin. In these lines there was an increase in expression of the mdr-1 gene which encodes P-glycoprotein, but not the mrp1 gene which encodes the multidrug resistance protein (MRP). The resistance was reversible using the MDR modulator PSC833, confirming the presence of P-glycoprotein. We conclude that MDM2 overexpression may be a mechanism by which multidrug resistance is regulated in some rhabdomyosarcomas. ? 2001 Cancer Research Campaign http://www.bjcancer.com
机译：已知MDM2蛋白在某些肉瘤（包括横纹肌肉瘤）中过表达。然而，尚不清楚MDM2蛋白影响对化疗药物敏感性的程度。我们已经使用mdm2基因稳定转染到4个特征明确的人小儿横纹肌肉瘤细胞系中进行了进一步分析。用mdm2基因转染导致所有细胞系中MDM2蛋白水平提高。在SCMC和RD中的2个品系中，mdm2基因引起对长春新碱，依托泊苷和阿霉素的耐药性提高了2倍至61倍，但对顺铂的耐药性却提高了2到61倍。在这些品系中，编码P-糖蛋白的mdr-1基因表达增加，但编码多药抗性蛋白（MRP）的mrp1基因表达没有增加。使用MDR调节剂PSC833可逆转耐药性，证实存在P-糖蛋白。我们得出结论，MDM2过表达可能是某些横纹肌肉瘤中通过调节多药耐药性的机制。 ？ 2001年癌症研究运动http://www.bjcancer.com

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