High levels of the MDM2 oncogene in paediatric rhabdomyosarcoma cell lines may confer multidrug resistance.
High levels of the MDM2 oncogene in paediatric rhabdomyosarcoma cell lines may confer multidrug resistance.
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DOI：
10.1054/bjoc.2001.2145
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发表时间：
2001-11-30
影响因子：
8.8
通讯作者：
Kelland LR
中科院分区：
文献类型：
--
作者：
Cocker HA;Hobbs SM;Tiffin N;Pritchard-Jones K;Pinkerton CR;Kelland LR
已知MDM 2蛋白在包括横纹肌肉瘤在内的一些肉瘤中过表达。然而，MDM 2蛋白影响化疗药物敏感性的程度尚不清楚。我们已经分析了这一点，进一步使用稳定转染mdm 2基因到4个良好的特点，人类小儿横纹肌肉瘤细胞系。用mdm 2基因转染导致所有细胞系中MDM 2蛋白水平增加。在其中2个细胞系SCMC和RD中，mdm 2基因导致对长春新碱、依托泊苷和多柔比星的耐药性增加2倍至61倍，但对顺铂的耐药性没有增加。在这些品系中，编码P-糖蛋白的mdr-1基因的表达增加，但编码多药耐药蛋白（MRP）的mrp 1基因的表达没有增加。使用MDR调节剂PSC 833，耐药性是可逆的，证实了P-糖蛋白的存在。我们的结论是，MDM 2的过度表达可能是一种机制，多药耐药的调节，在一些横纹肌肉瘤。© 2001年癌症研究运动http://www.bjcancer.com
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
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影响因子：
3.1
作者：
Li, ZY;Upadhyaya, NM;Waterhouse, PM
通讯作者：
Waterhouse, PM
DOI：
10.1159/000134368
发表时间：
1996-01-01
期刊：
CYTOGENETICS AND CELL GENETICS
影响因子：
--
作者：
Meddeb, M;Valent, A;Bernheim, A
通讯作者：
Bernheim, A
DOI：
10.1073/pnas.94.20.11037
发表时间：
1997-09-30
影响因子：
11.1
作者：
Thottassery, JV;Zambetti, GP;Schuetz, JD
通讯作者：
Schuetz, JD
影响因子：
45.3
作者：
CHAN, HSL;THORNER, PS;LING, V
通讯作者：
LING, V
影响因子：
3
作者：
Naito, M;Tsuruo, T
通讯作者：
Tsuruo, T