zeste基因增强子同源物2在乳腺癌中的研究现状
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摘要
zeste基因增强子同源物2(EZH2)是果蝇zeste基因增强子[E(z)]的人类同源物组蛋白甲基化的重要工具酶,也是多梳基因家族Pc G(polycomb group)的核心成员。EZH2参与多梳蛋白复合体2的形成,促使相应组蛋白甲基化,从表观遗传学的角度介导相应靶基因沉默,在肿瘤的发生、发展过程中发挥着重要作用。其高表达与多种恶性肿瘤的发生、发展和极差的预后密切相关。近年来,越来越多的学者对EZH2的致癌机制进行了深入研究,为乳腺癌转移的检测、预后评估及治疗提供了全新的思路。笔者就EZH2表达情况及其与乳腺癌发生、发展、转移及预后之间的关系作一综述,以便临床医师更好地认识这一新的肿瘤标志物。
引文
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[28]Yoo KH,Hennighausen L.EZH2 methyltransferase and H3K27methylation in breast cancer[J].Int J Biol Sci,2012,8(1):59-65.
[29]Li Z,Hou P,Fan D,et al.The degradation of EZH2 mediated by lncRNA ANCR attenuated the invasion and metastasis of breast cancer[J].Cell Death Differ,2017,24(1):59-71.
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[2]Lakhani SR,Ellis IO,Schnitt SJ,et al.World Health Organization classification of tumors of the breast[M].Lyon:IARC Press,2012:14.
[3]Ding L,Kleer CG.Enhancer of zeste 2 as a marker of preneoplastic progression in the breast[J].Cancer Res,2006,66(19):9352-9355.
[4]Bae WK,Hennighausen L.Canonical and non-canonical roles of the histone methyltransferase EZH2 in mammary development and cancer[J].Mol Cell Endocrinol,2014,382(1):593-597.
[5]姚响芸,王萌,薛丽香.Polycomb蛋白复合体对细胞衰老的表观遗传学调控[J].中国生物化学与分子生物学报,2012,28(4):304-309.
[6]Cavalli G.Molecular biology.EZH2 goes solo[J].Science,2012,338(6113):1430-1431.
[7]Hobert O,Jallal B,Ullrich A.Interaction of Vav with ENX-1,a putative transcriptional regulator of homeobox gene expression[J].Mol Cell Biol,1996,16(6):3066-3073.
[8]Cardoso C,Mignon C,Hetet G,et al.The human EZH2 gene:genomic organisation and revised mapping in 7q35 within the critical region for malignant myeloid disorders[J].Eur J Hum Genet,2000,8(3):174-180.
[9]Deb G,Singh AK,Gupta S.EZH2:not EZHY(easy)to deal[J].Mol Cancer Res,2014,12(5):639-653.
[10]Satijn DP,Otte AP.Polycomb group protein complexes:do different complexes regulate distinct target genes?[J].Biochim Biophys Acta,1999,1447(1):1-16.
[11]Cao R,Zhang Y.The functions of E(Z)/EZH2-mediated methylation of lysine 27 in histone H3[J].Curr Opin Genet Dev,2004,14(2):155-164.
[12]Visser HP,Gunster MJ,Kluin-Nelemans HC,et al.The polycomb group protein EZH2 is upregulated in proliferating,cultured human mantle cell lymphoma[J].Br J Haematol,2001,112(4):950-958.
[13]Zhang H,Qi J,Reyes JM,et al.Oncogenic deregulation of EZH2 as an opportunity for targeted therapy in lung cancer[J].Cancer Discov,2016,6(9):1006-1021.
[14]Cai MY,Tong ZT,Zheng F,et al.EZH2 protein:a promising immunomarker for the detection of hepatocellular carcinomas in liver needle biopsies[J].Gut,2011,60(7):967-976.
[15]Ozen C,Yildiz G,Dagcan AT,et al.Genetics and epigenetics of liver cancer[J].N Biotechnol,2013,30(4):381-384.
[16]Frankel AE,Liu X,Minna JD.Developing EZH2-targeted therapy for lung cancer[J].Cancer Discov,2016,6(9):949-952.
[17]Martínez-Fernández M,Rubio C,Segovia C,et al.EZH2 in bladder cancer,a promising therapeutic target[J].Int J Mol Sci,2015,16(11):27 107-27 132.
[18]Borbone E,Troncone G,Ferraro A,et al.Enhancer of zeste homolog 2overexpression has a role in the development of anaplastic thyroid carcinomas[J].J Clin Endocrinol Metab,2011,96(4):1029-1038.
[19]Jang SH,Lee JE,Oh MH,et al.High EZH2 protein expression is associated with poor overall survival in patients with luminal A breast cancer[J].J Breast Cancer,2016,19(1):53-60.
[20]Guo S,Li X,Rohr J,et al.EZH2 overexpression in different immunophenotypes of breast carcinoma and association with clinicopathologic features[J].Diagn Pathol,2016,11:41.
[21]Alford SH,Toy K,Merajver SD,et al.Increased risk for distant metastasis in patients with familial early-stage breast cancer and high EZH2 expression[J].Breast Cancer Res Treat,2012,132(2):429-437.
[22]Gong Y,Huo L,Liu P,et al.Polycomb group protein EZH2 is frequently expressed in inflammatory breast cancer and is predictive of worse clinical outcome[J].Cancer,2011,117(24):5476-5484.
[23]Collett K,Eide GE,Arnes J,et al.Expression of enhancer of zeste homologue 2 is significantly associated with increased tumor cell proliferation and is a marker of aggressive breast cancer[J].Clin Cancer Res,2006,12(4):1168-1174.
[24]Wang X,Hu B,Shen H,et al.Clinical and prognostic relevance of EZH2 in breast cancer:A meta-analysis[J].Biomed Pharmacother,2015,75:218-225.
[25]Knudsen ES,Dervishaj O,Kleer CG,et al.EZH2 and ALDH1expression in ductal carcinoma in situ:complex association with recurrence and progression to invasive breast cancer[J].Cell Cycle,2013,12(13):2042-2050.
[26]Wang L,Huang H.EZH2 takes the stage when BRCA1 loses[J].Cell Cycle,2013,12(23):3575-3576.
[27]Zhao L,Zhang QY,Luan X,et al.Relationship between the expression of Notch1 and EZH2 and the prognosis of breast invasive ductal carcinoma[J].Genet Mol Res,2016,15(1).doi:10.4238/gmr.15017464.
[28]Yoo KH,Hennighausen L.EZH2 methyltransferase and H3K27methylation in breast cancer[J].Int J Biol Sci,2012,8(1):59-65.
[29]Li Z,Hou P,Fan D,et al.The degradation of EZH2 mediated by lncRNA ANCR attenuated the invasion and metastasis of breast cancer[J].Cell Death Differ,2017,24(1):59-71.
[30]Jiang T,Wang Y,Zhou F,et al.Prognostic value of high EZH2expression in patients with different types of cancer:a systematic review with meta-analysis[J].Oncotarget,2016,7(4):4584-4597.
[31]严文君,冯爱强,张彦武,等.EZH2和CBX7在乳腺癌中的表达及其临床意义[J].中国普通外科杂志,2014,23(11):1512-1516.
[32]江泽飞,许凤锐.2016年乳腺癌精准医学发展:困境与出路[J/CD].中华乳腺病杂志(电子版),2017,11(2):65-68.