Haimeur A, Conseil G, Deeley R G, Cole S P C
Cancer Research Laboratories, Queen's University, Kingston, Ontario, Canada K7L 3N6.
Curr Drug Metab. 2004 Feb;5(1):21-53. doi: 10.2174/1389200043489199.
Several members of different families of the ATP-binding cassette (ABC) superfamily of transport proteins are capable of transporting an extraordinarily structurally diverse array of endo- and xenobiotics and their metabolites across cell membranes. Together, these transporters play an important role in the absorption, disposition and elimination of these chemicals in the body. In tumor cells, increased expression of these drug transporters is associated with resistance to multiple chemotherapeutic agents. In this review, current knowledge of the biochemical, physiological and pharmacological properties of nine members of the multidrug resistance protein (MRP)-related ABCC family (MRP1, MRP2, MRP3, MRP4, MRP5, MRP6, MRP7, ABCC11 and ABCC12) as well as the G family member, ABCG2/BCRP, are summarized. A focus is placed on the structural similarities and differences of these drug transporters as well as the molecular determinants of their substrate specificities and transport activities. Factors that regulate expression of the MRP-related proteins and ABCG2/BCRP are also reviewed.
ATP结合盒（ABC）超家族转运蛋白不同家族的几个成员能够跨细胞膜转运结构极其多样的内源性和外源性物质及其代谢产物。这些转运蛋白共同在体内这些化学物质的吸收、分布和消除中发挥重要作用。在肿瘤细胞中，这些药物转运蛋白的表达增加与对多种化疗药物的耐药性相关。在这篇综述中，总结了多药耐药蛋白（MRP）相关ABCC家族（MRP1、MRP2、MRP3、MRP4、MRP5、MRP6、MRP7、ABCC11和ABCC12）以及G家族成员ABCG2/BCRP的九个成员的生化、生理和药理特性的现有知识。重点关注这些药物转运蛋白的结构异同以及它们底物特异性和转运活性的分子决定因素。还综述了调节MRP相关蛋白和ABCG2/BCRP表达的因素。
