Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, Piscataway, NJ, USA.
Division of Toxicology, Environmental and Occupational Health Sciences Institute, Piscataway, NJ, USA.
Expert Opin Drug Metab Toxicol. 2020 Mar;16(3):239-253. doi: 10.1080/17425255.2020.1732348. Epub 2020 Mar 14.
: The breast cancer resistance protein (BCRP/) is a member of the ATP-binding cassette superfamily of transporters. Using the energy garnered from the hydrolysis of ATP, BCRP actively removes drugs and endogenous molecules from the cell. With broad expression across the liver, kidney, brain, placenta, testes, and small intestines, BCRP can impact the pharmacokinetics and pharmacodynamics of xenobiotics.: The purpose of this review is to summarize the transcriptional signaling pathways that regulate BCRP expression across various tissues and mammalian species. We will cover the endobiotic- and xenobiotic-activated transcription factors that regulate the expression and activity of BCRP. These include the estrogen receptor, progesterone receptor, peroxisome proliferator-activated receptor, constitutive androstane receptor, pregnane X receptor, nuclear factor e2-related factor 2, and aryl hydrocarbon receptor.: Key transcription factors regulate BCRP expression and function in response to hormones and xenobiotics. Understanding this regulation provides an opportunity to improve pharmacotherapeutic outcomes by enhancing the efficacy and reducing the toxicity of drugs that are substrates of this efflux transporter.
: 乳腺癌耐药蛋白（BCRP）是 ATP 结合盒转运体超家族的成员。BCRP 通过利用 ATP 水解产生的能量，将药物和内源性分子从细胞中主动排出。BCRP 在肝脏、肾脏、大脑、胎盘、睾丸和小肠中广泛表达，可影响外源性物质的药代动力学和药效学。: 本综述的目的是总结调节 BCRP 在各种组织和哺乳动物物种中表达的转录信号通路。我们将介绍调节 BCRP 表达和活性的内源性和外源性激活转录因子。这些包括雌激素受体、孕激素受体、过氧化物酶体增殖物激活受体、组成型雄烷受体、孕烷 X 受体、核因子 E2 相关因子 2 和芳烃受体。: 关键转录因子可调节 BCRP 的表达和功能，以响应激素和外源性物质。了解这种调节为提高药物治疗效果提供了机会，可通过增强该外排转运体底物的疗效和降低其毒性来实现。
