title: Structure and function of the human breast cancer resistance protein (BCRP/ABCG2).
abstract: The human breast cancer resistance protein (BCRP/ABCG2) is the second member of the G subfamily of the large ATP-binding cassette (ABC) transporter superfamily. BCRP was initially discovered in multidrug resistant breast cancer cell lines where it confers resistance to chemotherapeutic agents such as mitoxantrone, topotecan and methotrexate by extruding these compounds out of the cell. BCRP is capable of transporting non-chemotherapy drugs and xenobiotiocs as well, including nitrofurantoin, prazosin, glyburide, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. BCRP is frequently detected at high levels in stem cells, likely providing xenobiotic protection. BCRP is also highly expressed in normal human tissues including the small intestine, liver, brain endothelium, and placenta. Therefore, BCRP has been increasingly recognized for its important role in the absorption, elimination, and tissue distribution of drugs and xenobiotics. At present, little is known about the transport mechanism of BCRP, particularly how it recognizes and transports a large number of structurally and chemically unrelated drugs and xenobiotics. Here, we review current knowledge of structure and function of this medically important ABC efflux drug transporter.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, University of Washington, Health Science Building H272, 1959 NE Pacific Street, Seattle, Washington 98195-7610, USA.
authors.forename: Zhanglin
authors.initials: Z
authors.lastname: Ni
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Bikadi
authors.forename: Mark F
authors.initials: MF
authors.lastname: Rosenberg
authors.forename: Qingcheng
authors.initials: Q
authors.lastname: Mao
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics; D018432:Drug Resistance, Multiple / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D050505:Mutant Proteins / Q000378:metabolism / Q000502:physiology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D040681:Structural Homology, Protein; D013379:Substrate Specificity; D015262:Xenobiotics / Q000493:pharmacokinetics
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D050505:Mutant Proteins; D009363:Neoplasm Proteins; D015262:Xenobiotics
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