de Silva M, Kantharidis P, Wall D M, Campbell L, Vrazas V, Nadalin G, Kaczmarczyk S J, Hu X F, Parkin J D, Zalcberg J R
Department of Medical Oncology, Austin & Repatriation Medical Centre, Victoria, Australia.
Br J Cancer. 1996 Jan;73(2):169-74. doi: 10.1038/bjc.1996.31.
A major form of drug resistance in tumour cells known as classical multidrug resistance (MDR) is associated with the overexpression of the mdr1 gene product, the membrane protein P-glycoprotein (P-gp), which acts as an energy-dependent drug efflux pump. In this study the inheritance of P-gp expression was examined using hybrids formed after somatic cell fusion between a drug-sensitive human T-cell leukaemia cell line, CEM/CCRF, and a drug-resistant derivative, CEM/A7, which is characterized by a clonal chromosomal duplication dup(7)(q11.23q31.2). Fourteen hybrids, chosen at random, were analysed by reverse transcriptase-polymerase chain reaction (RT-PCR) and by binding studies involving the monoclonal antibody MRK16, which recognises an external P-gp epitope. Only two hybrids were positive for both MRK16 antibody labelling and mdr1 mRNA. Partial karyotypic analysis of all hybrids revealed that only the MRK16-positive hybrids contained the duplication in chromosome 7 seen in the CEM/A7 parental MDR line. Therefore, P-gp overexpression in the MRK16-positive hybrids may be linked to the inheritance of chromosome 7 from CEM/A7 and possibly associated with the chromosome 7 abnormality.
肿瘤细胞中一种主要的耐药形式称为经典多药耐药（MDR），它与mdr1基因产物膜蛋白P-糖蛋白（P-gp）的过表达有关，P-糖蛋白作为一种能量依赖型药物外排泵发挥作用。在本研究中，利用药物敏感的人T细胞白血病细胞系CEM/CCRF与耐药衍生物CEM/A7进行体细胞融合后形成的杂种细胞，检测P-糖蛋白表达的遗传情况，CEM/A7的特征是克隆性染色体重复dup(7)(q11.23q31.2)。随机选择14个杂种细胞，通过逆转录聚合酶链反应（RT-PCR）和涉及单克隆抗体MRK16的结合研究进行分析，MRK16识别P-糖蛋白的一个外部表位。只有两个杂种细胞对MRK16抗体标记和mdr1 mRNA均呈阳性。对所有杂种细胞的部分核型分析表明，只有MRK16阳性的杂种细胞含有在CEM/A7亲本MDR细胞系中看到的7号染色体重复。因此，MRK16阳性杂种细胞中P-糖蛋白的过表达可能与来自CEM/A7的7号染色体遗传有关，并可能与7号染色体异常相关。
