在选择出的对高剂量甲氨蝶呤耐药的CCRF-CEM细胞中的非典型多药耐药性：在无P-糖蛋白表达情况下对单克隆抗体C219的反应性

Atypical multidrug resistance in CCRF-CEM cells selected for high level methotrexate resistance: reactivity to monoclonal antibody C219 in the absence of P-glycoprotein expression.

作者信息

Norris M D, Haber M, King M, Davey R A

机构信息

Children's Leukaemia and Cancer Research Unit, Prince of Wales Children's Hospital, Sydney, Australia.

出版信息

Biochem Biophys Res Commun. 1989 Dec 29;165(3):1435-41. doi: 10.1016/0006-291x(89)92764-2.

DOI:10.1016/0006-291x(89)92764-2

PMID:2575383

Abstract

A series of CCRF-CEM sublines selected for extreme resistance to methotrexate has been shown previously to exhibit cross resistance to a number of agents belonging to the multidrug resistance phenotype (J.Natl.Cancer Inst.1989; 81, 1250-1254). The role of the mdr1 gene and its product (P-glycoprotein) in this atypical pattern of multidrug resistance has now been investigated. Southern and Northern analyses failed to demonstrate any amplification, rearrangement or over-expression of the mdr1 gene in the drug-resistant cells. Similarly, monoclonal antibodies MRK16 and JSB1 revealed no increase in the amount of P-glycoprotein present. By contrast, monoclonal antibody C219 detected a 170 kDa protein in all sublines, and in highest concentration in the most resistant cells. The results raise the possibility that a novel, C219-reactive protein may mediate resistance to both methotrexate and members of the multidrug resistance family.

摘要

先前已证明，一系列经选择对甲氨蝶呤具有极强抗性的CCRF-CEM亚系，对多种属于多药耐药表型的药物表现出交叉抗性（《美国国家癌症研究所杂志》1989年；81卷，1250 - 1254页）。现在已经对mdr1基因及其产物（P-糖蛋白）在这种非典型多药耐药模式中的作用进行了研究。Southern印迹分析和Northern印迹分析未能证明耐药细胞中mdr1基因有任何扩增、重排或过表达。同样，单克隆抗体MRK16和JSB1显示，所存在的P-糖蛋白量没有增加。相比之下，单克隆抗体C219在所有亚系中都检测到一种170 kDa的蛋白质，且在抗性最强的细胞中浓度最高。这些结果提示，一种新的、与C219反应的蛋白质可能介导对甲氨蝶呤和多药耐药家族成员的抗性。