乳腺癌耐药蛋白基因的转录调控机制-遗传.pdfVIP

HEREDITAS (Beijing) 2012 12 , 34(12): 1529―1536 ISSN 0253-9772 综 述 DOI: 10.3724/SP.J.1005.2012.01529 乳腺癌耐药蛋白基因的转录调控机制 吴新刚, 彭姝彬, 黄谦 , 414000 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。 乳腺癌耐药蛋白; 转录调控; DNA 甲基化; 转录因子; 多药耐药 Transcriptional regulation of breast cancer resistance protein WU Xin-Gang, PENG Shu-Bin, HUANG Qian Department of Basic Medical Sciences , Yueyang Higher Vocational and Technical College, Yueyang 414000, China Abstract: 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 transcript