title: ABCC10, ABCC11, and ABCC12.
abstract: Multidrug resistance protein (MRP)7, MRP8, and MRP9 (gene symbols ABCC10, ABCC11, and ABCC12) are recently identified members of the MRP family that are at relatively early stages of investigation. Of these proteins, a physiological function has only been established for MRP8, for which a single nucleotide polymorphism determines wet vs dry earwax type. MRP7 and MRP8 are lipophilic anion pumps that are able to confer resistance to chemotherapeutic agents. MRP7 is competent in the transport of the glucuronide E(2)17betaG, and its resistance profile, which includes several natural product anticancer agents, is distinguished by the taxane docetaxel. MRP8 is able to transport a diverse range of lipophilic anions, including cyclic nucleotides, E(2)17betaG, steroid sulfates such as dehydroepiandrosterone (DHEAS) and E(1)S, glutathione conjugates such as leukotriene C4 and dinitrophenyl-S-glutathione, and monoanionic bile acids. However, the constituent of earwax that is susceptible to transport by MRP8 has not been identified. MRP8 has complex interactions with its substrates, as indicated by the nonreciprocal ability of DHEAS to stimulate E(2)17betaG transport. Similar to the case for other MRPs that possess only two membrane spanning domains (MRP4 and MRP5), MRP8 is a cyclic nucleotide efflux pump that is able to confer resistance to nucleoside-based agents, such as PMEA and 5FU. The functional characteristics of MRP9 are currently unknown.
authors.affiliation: Medical Science Division, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. Gary.Kruh@fccc.edu
authors.forename: Gary D
authors.initials: GD
authors.lastname: Kruh
authors.forename: Yanping
authors.initials: Y
authors.lastname: Guo
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hopper-Borge
authors.forename: Martin G
authors.initials: MG
authors.lastname: Belinsky
authors.forename: Zhe-Sheng
authors.initials: ZS
authors.lastname: Chen
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000818:Animals; D002571:Cerumen / Q000502:physiology; D019314:Dehydroepiandrosterone Sulfate / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D005786:Gene Expression Regulation; D006801:Humans; D008727:Methotrexate / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000502:physiology*; D009369:Neoplasms / Q000503:physiopathology; D009712:Nucleotides, Cyclic / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D018528:ATP-Binding Cassette Transporters; D019314:Dehydroepiandrosterone Sulfate; D008727:Methotrexate; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009712:Nucleotides, Cyclic; C421142:ABCC10 protein, human; C435500:ABCC11 protein, human; C435501:ABCC12 protein, human