Human multidrug resistance protein 7 (ABCC10) is a resistance factor for nucleoside analogues and epothilone B.

Cancer Research
Elizabeth A Hopper-BorgeGary D Kruh

Abstract

Multidrug resistance protein 7 (MRP7; ABCC10) is an ATP-binding cassette transporter which is able to transport amphipathic anions and confer resistance to docetaxel and, to a lesser extent, vincristine and paclitaxel. Whereas some detail on the resistance profile of MRP7 is known, the activities of the pump have not been completely determined. Here, it is shown by the analysis of MRP7-transfected HEK293 cells that, in addition to natural product agents, MRP7 is also able to confer resistance to nucleoside-based agents, such as the anticancer agents cytarabine (Ara-C) and gemcitabine, and the antiviral agents 2',3'-dideoxycytidine and PMEA. Consistent with the operation of an efflux pump, expression of MRP7 reduced the accumulation of Ara-C and PMEA. In addition, MRP7 is also able to confer resistance to the microtubule-stabilizing agent epothilone B. Ectopic expression of MRP7 in mouse embryo fibroblasts deficient in P-glycoprotein and Mrp1 revealed that MRP7 has a broad resistance profile for natural product agents. In this drug-sensitive cellular background, MRP7 conferred high levels of resistance to docetaxel (46-fold), paclitaxel (116-fold), SN-38 (65-fold), daunorubicin (7.5-fold), etoposide (11-fold), and vincristine (5...Continue Reading

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