乳腺癌耐药蛋白基因的转录调控机制  

Transcriptional regulation of breast cancer resistance protein

作　　者：吴新刚[1] 彭姝彬[1] 黄谦[1] 

机构地区：[1]岳阳职业技术学院医学基础部,岳阳414000

出　　处：《遗传》2012年第12期1529-1536,共8页Hereditas（Beijing)

基　　金：岳阳职业技术学院(编号:YZ1104G);湖南省教育厅项目(编号:11C1284)资助

摘　　要：乳腺癌耐药蛋白(Breast cancer resistance protein,BCRP),又名ABCG2,是ATP结合盒(ATP-binding cas-sette,ABC)转运蛋白超家族成员之一,在肿瘤多药耐药中具有十分重要的作用。BCRP基因启动子区无TATA盒,含CAAT盒、AP1位点、AP2位点以及CpG岛下游的多个Sp-1位点。近年来的研究发现,转录因子孕激素受体(PR)、雌激素受体(ER)、核因子-κB(NF-κB)、缺氧诱导因子(HIF)、Nrf2、芳香烃受体(AhR)、过氧化物酶体增殖活化受体(PPAR)和KLF5等可与BCRP启动子或增强子区的特定反应元件结合进而激活BCRP的转录。促炎细胞因子、生长因子、同源盒基因MSX2、Sonic hedgehog信号通路、Notch信号通路和RAR/RXR信号通路等均参与了BCRP的转录调控。此外,启动子甲基化和组蛋白乙酰化在BCRP转录调控尤其是药物诱导BCRP表达中发挥重要作用。文章综述了这一研究领域的进展,着重讨论了转录因子及表观遗传学在BCRP转录调控中的作用。Breast cancer resistance protein（BCRP）,also known as ABCG2,is a member of the ATP-binding cassette（ABC） transporter superfamily,and is known to play important roles in cancer multidrug resistance.The BCRP promoter lacks a TATA-box and contains a CAAT-box,lots of AP1,AP2 sites and several putative Sp1 sites which are downstream of a putative CpG island.Several transcription factors,such as progesterone receptor（PR）,estrogen receptor（ER）,nuclear factor-κB（NF-κB）,hypoxia-inducible factors（HIFs）,nuclear factor erythroid 2-related factor 2（Nrf2）,aryl hydrocarbon receptor（AhR）,peroxisome proliferator-activated receptors（PPARs） and Krüppel-like factor 5（KLF5）,have been recently shown to bind to their response elements in the promoter/enhancer to activate the transcription of BCRP.BCRP transcription can be influenced by proinflammatory cytokines,growth factors,and homeobox protein MSX2.Signaling pathways,such as Sonic hedgehog（Shh）,Notch and RAR/RXR pathways,may also involve in the transcriptional regulation of BCRP.In addition,promoter methylation and histone acetylation are essential for the BCRP transcription,especially for the drug-induced BCRP expression.This paper reviews the recent research progresses in this field with an emphasis on the roles of transcription factors and epigenetics in the transcriptional regulation of BCRP.

关 键 词：乳腺癌耐药蛋白 转录调控 DNA甲基化 转录因子 多药耐药 

分 类 号：R737.9[医药卫生—肿瘤]