Role of breast cancer resistance protein (BCRP/ABCG2) in cancer drug resistance

详细信息	查看全文 | 推荐本文 |

• 作者：Karthika Natarajan^a ; Yi Xie^a ; Maria R. Baer^a ; ^b ; Douglas D. Ross^a ; ^b ; ^c ; ^d ; ^{dross@som.umaryland.edu}
• 关键词：ATP binding cassette transporters ; Breast cancer resistance protein ; ABCG2 ; Drug absorption ; distribution ; metabolism and excretion ; Cancer ; Drug resistance
• 刊名：Biochemical Pharmacology
• 出版年：2012
• 期刊代码：2_00062952
• 类别：pha
• 出版时间：15 April, 2012
• 卷：83
• 期：8
• 页码：1084-1103
• 文件大小：1093 K

摘要

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 鈥渟ide population cells,鈥?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 鈥渟ide population鈥?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.