University of Maryland Greenebaum Cancer Center, Baltimore, MD 21201, USA.
Biochem Pharmacol. 2012 Apr 15;83(8):1084-103. doi: 10.1016/j.bcp.2012.01.002. Epub 2012 Jan 11.
Since cloning of the ATP-binding cassette (ABC) family member breast cancer resistance protein (BCRP/ABCG2) and its characterization as a multidrug resistance efflux transporter in 1998, BCRP has been the subject of more than two thousand scholarly articles. In normal tissues, BCRP functions as a defense mechanism against toxins and xenobiotics, with expression in the gut, bile canaliculi, placenta, blood-testis and blood-brain barriers facilitating excretion and limiting absorption of potentially toxic substrate molecules, including many cancer chemotherapeutic drugs. BCRP also plays a key role in heme and folate homeostasis, which may help normal cells survive under conditions of hypoxia. BCRP expression appears to be a characteristic of certain normal tissue stem cells termed "side population cells," which are identified on flow cytometric analysis by their ability to exclude Hoechst 33342, a BCRP substrate fluorescent dye. Hence, BCRP expression may contribute to the natural resistance and longevity of these normal stem cells. Malignant tissues can exploit the properties of BCRP to survive hypoxia and to evade exposure to chemotherapeutic drugs. Evidence is mounting that many cancers display subpopulations of stem cells that are responsible for tumor self-renewal. Such stem cells frequently manifest the "side population" phenotype characterized by expression of BCRP and other ABC transporters. Along with other factors, these transporters may contribute to the inherent resistance of these neoplasms and their failure to be cured.
自 1998 年克隆 ATP 结合盒（ABC）家族成员乳腺癌耐药蛋白（BCRP/ABCG2）并将其鉴定为多药耐药外排转运蛋白以来，BCRP 已成为两千多篇学术文章的主题。在正常组织中，BCRP 作为一种防御机制，对抗毒素和外源性物质，在肠道、胆小管、胎盘、血睾和血脑屏障中表达，促进排泄并限制潜在毒性底物分子的吸收，包括许多癌症化疗药物。BCRP 还在血红素和叶酸稳态中发挥关键作用，这有助于正常细胞在缺氧条件下存活。BCRP 表达似乎是某些正常组织干细胞的特征，这些干细胞被称为“侧群细胞”，它们在流式细胞分析中通过其排除 BCRP 底物荧光染料 Hoechst 33342 的能力来识别。因此，BCRP 表达可能有助于这些正常干细胞的自然耐药性和长寿性。恶性组织可以利用 BCRP 的特性来在缺氧环境中存活，并逃避化疗药物的暴露。越来越多的证据表明，许多癌症显示出负责肿瘤自我更新的干细胞亚群。这些干细胞经常表现出 BCRP 和其他 ABC 转运蛋白表达的“侧群”表型。这些转运蛋白与其他因素一起，可能导致这些肿瘤的固有耐药性及其无法治愈。
