Epitope mapping of monoclonal antibodies specific for the 190-kDa multidrug resistance protein (MRP)

被引:71
作者
Hipfner, DR
Gao, M
Scheffer, G
Scheper, RJ
Deeley, RG
Cole, SPC [1 ]
机构
[1] Queens Univ, Canc Res Labs, Kingston, ON K7L 3N6, Canada
[2] Queens Univ, Dept Pathol, Kingston, ON K7L 3N6, Canada
[3] Free Univ Amsterdam Hosp, Dept Pathol, NL-1081 HV Amsterdam, Netherlands
基金
英国医学研究理事会;
关键词
multidrug resistance; multidrug resistance protein; monoclonal antibody; epitope mapping;
D O I
10.1038/bjc.1998.642
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Inherent or acquired resistance to multiple natural product drugs in human tumour cells is often associated with increased expression of multidrug resistance protein (MRP), a 190-kDa integral membrane protein that belongs to the ATP-binding cassette (ABC) superfamily of transport proteins. Both clinical and experimental investigations of MRP have been facilitated by several monoclonal antibodies (MAbs) generated against intracellular epitopes of the molecule. Recently, however, several new ABC transporters that are quite closely related to MRP have been identified, raising concerns about the specificity of the MRP-reactive MAbs, In the present study, we have mapped the epitopes of MAbs MRPr1 and MRPm6 to the decapeptides (238)GSDLWSLNKE(247) (located in the intracellular loop between the first and second membrane-spanning domains of MRP) and (1511)PSDLLQQRGL(1520) (located near the carboxy terminus of MRP) respectively. Alignment of the MRPr1 and MRPm6 epitope sequences with the comparable regions in mammalian ABC proteins most closely related to MRP indicates that, with the exception of murine mrp, the sequences are poorly conserved. We conclude that MAbs MRPm6 and MRPr1, together with MAb QCRL-1, which has previously been mapped to the heptapeptide (918)SSYSGD(924), remain highly specific probes for detection of different regions of the MRP molecule.
引用
收藏
页码:1134 / 1140
页数:7
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