ABCG2: a perspective.
ABCG2: a perspective.
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DOI：
10.1016/j.addr.2008.11.003
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发表时间：
2009-01-31
影响因子：
16.1
通讯作者：
Bates, Susan E.
中科院分区：
文献类型：
--
作者：
Robey, Robert W.;To, Kenneth K. K.;Polgar, Orsolya;Dohse, Marius;Fetsch, Patricia;Dean, Michael;Bates, Susan E.
ABCG2，或乳腺癌耐药蛋白(BCRP)，是一种ABC转运蛋白，自十年前发现以来一直是密集研究的主题。ABCG2在脑内皮细胞、胃肠道和胎盘中有较高的正常组织表达，被认为在保护外源物质、调节口服生物利用度、形成血脑屏障、血睾丸屏障和母胎屏障方面具有重要作用。值得注意的是，ABCG2经常在干细胞群体中表达，在那里它可能在异种生物保护中发挥作用。然而，关于它在各种细胞群体中的表观遗传调控的线索才刚刚开始出现。虽然ABCG2在体外药物治疗后的癌细胞中有过表达，但某些癌症中内源性ABCG2的表达可能反映了起源细胞的分化表型，并可能与内在耐药有关。值得注意的是，关于转运蛋白在癌症耐药中的作用及其作为癌症治疗靶点的发展的研究一直滞后。已经描述了转运蛋白的底物和抑制剂，其中包括化疗药物、酪氨酸激酶抑制剂、抗病毒药物、HMG-CoA还原酶抑制剂、致癌物和类黄酮类化合物。这种广泛的底物范围补充了ABCG2在实验室研究中作为转运蛋白的效率，并表明，尽管存在多余的异种保护机制，但蛋白质在正常生理中是重要的。事实上，药理学和毒理学中评估人类多态变异的新研究，结合小鼠基因敲除模型，已经证实了它的动态作用。药理学方面的工作可能最终会让我们更好地理解ABCG2的生理作用。
ABCG2, or Breast Cancer Resistance Protein (BCRP), is an ABC transporter that has been the subject of intense study since its discovery a decade ago. With high normal tissue expression in the brain endothelium, gastrointestinal tract, and placenta, ABCG2 is believed to be important in protection from xenobiotics, regulating oral bioavailability, forming part of the blood-brain barrier, the blood-testis barrier, and the maternal-fetal barrier. Notably, ABCG2 is often expressed in stem cell populations, where it likely plays a role in xenobiotic protection. However, clues to its epigenetic regulation in various cell populations are only beginning to emerge. While ABCG2 overexpression has been demonstrated in cancer cells after in vitro drug treatment, endogenous ABCG2 expression in certain cancers is likely a reflection of the differentiated phenotype of the cell of origin and likely contributes to intrinsic drug resistance. Notably, research into the transporter’s role in cancer drug resistance and its development as a therapeutic target in cancer has lagged. Substrates and inhibitors of the transporter have been described, among them chemotherapy drugs, tyrosine kinase inhibitors, antivirals, HMG-CoA reductase inhibitors, carcinogens, and flavonoids. This broad range of substrates complements the efficiency of ABCG2 as a transporter in laboratory studies and suggests that, while there are redundant mechanisms of xenobiotic protection, the protein is important in normal physiology. Indeed, emerging studies in pharmacology and toxicology assessing polymorphic variants in man, in combination with murine knockout models have confirmed its dynamic role. Work in pharmacology may eventually lead us to a greater understanding of the physiologic role of ABCG2.
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影响因子：
11.4
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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作者：
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