乳腺癌耐药蛋白基因的转录调控机制

doi:10.3724/SP.J.1005.2012.01529

遗传 ›› 2012, Vol. 34 ›› Issue (12): 1529-1536.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

岳阳职业技术学院医学基础部, 岳阳 414000

收稿日期:2012-03-20 修回日期:2012-05-11 出版日期:2012-12-20 发布日期:2012-12-25
通讯作者: 吴新刚 E-mail:wu_alwin@yahoo.com.cn
基金资助:
岳阳职业技术学院(编号：YZ1104G)和湖南省教育厅项目(编号：11C1284)资助

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

Received:2012-03-20 Revised:2012-05-11 Online:2012-12-20 Published:2012-12-25

摘要/Abstract

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。

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

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 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.

Key words: breast cancer resistance protein (BCRP), transcriptional regulation, DNA methylation, transcription factors, multidrug resistance(MDR)

吴新刚，彭姝彬，黄谦. 乳腺癌耐药蛋白基因的转录调控机制[J]. 遗传, 2012, 34(12): 1529-1536.

WU Xin-Gang PENG Shu-Bin HUANG Qian. Transcriptional regulation of breast cancer resistance protein[J]. HEREDITAS, 2012, 34(12): 1529-1536.

参考文献

[1] Doyle LA, Yang WD, Abruzzo LV, Krogmann T, Gao YM, Rishi AK, Ross DD. A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci USA, 1998, 95(26): 15665-15670.
[2] Natarajan K, Xie Y, Baer MR, Ross DD. Role of breast cancer resistance protein (BCRP/ABCG2) in cancer drug resistance. Biochem Pharmacol, 2012, 83(8): 1084-1103.
[3] Noguchi K, Katayama K, Mitsuhashi J, Sugimoto Y. Functions of the breast cancer resistance protein (BCRP/ABCG2) in chemotherapy. Adv Drug Deliv Rev, 2009, 61(1): 26-33.
[4] Wang H, Lee EW, Zhou L, Leung PC, Ross DD, Unadkat JD, Mao Q. Progesterone receptor (PR) isoforms PRA and PRB differentially regulate expression of the breast cancer resistance protein in human placental choriocarcinoma BeWo cells. Mol Pharmacol, 2008, 73(3): 845-854.
[5] Evseenko DA, Paxton JW, Keelan JA. Independent regulation of apical and basolateral drug transporter expression and function in placental trophoblasts by cytokines, ster-oids, and growth factors. Drug Metab Dispos, 2007, 35(4): 595-601.
[6] Yasuda S, Kobayashi M, Itagaki S, Hirano T, Iseki K. Response of the ABCG2 promoter in T47D cells and BeWo cells to sex hormone treatment. Mol Biol Rep, 2009, 36(7): 1889-1896.
[7] Wu XJ, Zhang XF, Zhang H, Su P, Li WW, Li L, Wang Y, Liu WJ, Gao P, Zhou GY. Progesterone receptor down-regulates breast cancer resistance protein expression via binding to the progesterone response element in breast cancer. Cancer Sci, 2012, 103(5): 959-967.
[8] Zhang YH, Wang HP, Wei LJ, Li G, Yu J, Gao Y, Gao P, Zhang XF, Wei FL, Yin DL, Zhou GY. Transcriptional modulation of BCRP gene to reverse multidrug resistance by toremifene in breast adenocarcinoma cells. Breast Cancer Res Treat, 2010, 123(3): 679-689.
[9] Hartz AMS, Madole EK, Miller DS, Bauer B. Estrogen receptor β signaling through phosphatase and tensin ho-molog/phosphoinositide 3-kinase/Akt/glycogen synthase kinase 3 down-regulates blood-brain barrier breast cancer resistance protein. J Pharmacol Exp Ther, 2010, 334(2): 467-476.
[10] Wang HG, Unadkat JD, Mao QC. Hormonal regulation of BCRP expression in human placental BeWo cells. Pharm Res, 2008, 25(2): 444-452.
[11] Wang XD, Wu XG, Wang CK, Zhang WJ, Ouyang YM, Yu YH, He ZM. Transcriptional suppression of breast cancer resistance protein (BCRP) by wild-type p53 through the NF-κB pathway in MCF-7 cells. FEBS Lett, 2010, 584(15): 3392-3397.
[12] 吴新刚, 彭姝彬, 闾四平, 张年凤, 邹进. p53对乳腺癌耐药蛋白基因的转录调控. 中国生物化学与分子生物学报, 2012, 28(2): 152-157.
[13] Zhang WJ, Ding W, Chen Y, Feng ML, Ouyang YM, Yu YH, He ZM. Up-regulation of breast cancer resistance protein plays a role in HER2-mediated chemoresistance through PI3K/Akt and nuclear factor-κB signaling path-ways in MCF7 breast cancer cells. Acta Biochim Biophys Sin, 2011, 43(8): 647-653.
[14] Krishnamurthy P, Ross DD, Nakanishi T, Bailey-Dell K, Zhou S, Mercer KE, Sarkadi B, Sorrentino BP, Schuetz JD. The stem cell marker Bcrp/ABCG2 enhances hypoxic cell survival through interactions with heme. J Biol Chem, 2004, 279(23): 24218-24225.
[15] Martin CM, Ferdous A, Gallardo T, Humphries C, Sadek H, Caprioli A, Garcia JA, Szweda LI, Garry MG, Garry DJ. Hypoxia-inducible factor-2α transactivates Abcg2 and promotes cytoprotection in cardiac side population cells. Circ Res, 2008, 102(9): 1075-1081.
[16] Reisman SA, Yeager RL, Yamamoto M, Klaassen CD. In-creased Nrf2 activation in livers from Keap1-knockdown mice increases expression of cytoprotective genes that detoxify electrophiles more than those that detoxify reactive oxygen species. Toxicol Sci, 2009, 108(1): 35-47.
[17] Singh A, Wu HL, Zhang P, Happel C, Ma JF, Biswal S. Expression of ABCG2 (BCRP) is regulated by Nrf2 in cancer cells that confers side population and chemoresistance phenotype. Mol Cancer Ther

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乳腺癌耐药蛋白基因的转录调控机制

Transcriptional regulation of breast cancer resistance protein

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