Department of Pharmaceutics, School of Pharmacy, University of Washington, Health Science Building H272, 1959 NE Pacific Street, Seattle, Washington 98195-7610, USA.
Curr Drug Metab. 2010 Sep;11(7):603-17. doi: 10.2174/138920010792927325.
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.
人乳腺癌耐药蛋白（BCRP/ABCG2）是大 ATP 结合盒（ABC）转运体超家族 G 亚家族的第二个成员。BCRP 最初在多药耐药乳腺癌细胞系中发现，它通过将这些化合物从细胞内排出，使细胞对化疗药物如米托蒽醌、拓扑替康和甲氨蝶呤产生耐药性。BCRP 还能够转运非化疗药物和外源性化合物，包括呋喃妥因、普萘洛尔、格列吡嗪和 2-氨基-1-甲基-6-苯基咪唑[4,5-b]吡啶。BCRP 在干细胞中高水平表达，可能为外源性化合物提供保护。BCRP 在正常人体组织中也高度表达，包括小肠、肝脏、脑内皮和胎盘。因此，BCRP 因其在药物和外源性化合物的吸收、消除和组织分布中的重要作用而受到越来越多的关注。目前，人们对 BCRP 的转运机制知之甚少，特别是它如何识别和转运大量结构和化学上无关的药物和外源性化合物。本文综述了该具有重要医学意义的 ABC 外排药物转运体的结构和功能的最新知识。
