组蛋白修饰在乳腺癌中的研究进展

doi:10.3760/cma.j.issn.1673-422X.2017.10.013

摘要/Abstract

摘要： 在乳腺癌研究中，表观遗传调控起了重要的作用。其中，组蛋白的表观遗传修饰主要是在各种酶类的作用下，通过加入和去除甲基、乙酰基以及磷酸基团等来影响乳腺癌的发生发展。由于其调控变化过程是可逆的，可以为受影响的区域恢复到正常的基因组状态提供优势。临床上可以利用这一点开发各种药物来用于患者的诊疗，并提供治疗靶点。

关键词: 后成说, 遗传, 组蛋白类, 乳腺肿瘤

Abstract: Epigenetic regulation plays an important role in breast cancer research. The epigenetic modification of histone mainly affects the occurrence and development of breast cancer by adding and removing methyl, acetyl and phosphate groups under the action of various enzymes. Because of its reversible regulatory process, it can provide advantage for the affected region to return to the normal genome state. Clinically, this can be used to develop a variety of drugs for patient diagnosis and treatment and to provide treatment targets.

Key words: Epigenesis, genetic, Histones, Breast neoplasms

房佳慧,王长山,贾永峰. 组蛋白修饰在乳腺癌中的研究进展[J]. 国际肿瘤学杂志, 2017, 44(10): 775-778.

Fang Jiahui, Wang Changshan, Jia Yongfeng. Histone modification in breast cancer[J]. Journal of International Oncology, 2017, 44(10): 775-778.

参考文献

［1］ Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015［J］. CA Cancer J Clin, 2016, 66(2): 115132. DOI: 10.3322/caac.21338. ［2］ Kanwal R, Gupta S. Epigenetic modifications in cancer［J］. Clin Genet, 2012, 81(4): 303311. DOI: 10.1111/j.13990004.2011.01809.x. ［3］ Yen CY, Huang HW, Shu CW, et al. DNA methylation, histone acetylation and methylation of epigenetic modifications as a therapeutic approach for cancers［J］. Cancer Lett, 2016, 373(2): 185192. DOI: 10.1016/j.canlet.2016.01.036. ［4］ Rose NR, Klose RJ. Understanding the relationship between DNA methylation and histone lysine methylation［J］. Biochim Biophys Acta, 2014, 1839(12): 13621372. DOI: 10.1016/j.bbagrm.2014.02.007. ［5］ Liu Y, Liu K, Qin S, et al. Epigenetic targets and drug discovery: part 1: histone methylation［J］. Pharmacol Ther, 2014, 143(3): 275294. DOI: 10.1016/j.pharmthera.2014.03.007. ［6］ McGrath J, Trojer P. Targeting histone lysine methylation in cancer［J］. Pharmacol Ther, 2015, 150: 122. DOI: 10.1016/j.pharmthera.2015.01.002. ［7］ Chou RH, Chiu L, Yu YL, et al. The potential roles of EZH2 in regenerative medicine［J］. Cell Transplant, 2015, 24(3): 313317. DOI: 10.3727/096368915X686823. ［8］ Vlkel P, Dupret B, Le Bourhis X, et al. Diverse involvement of EZH2 in cancer epigenetics［J］. Am J Transl Res, 2015, 7(2): 175193. ［9］ Chou RH, Chiu L, Yu YL, et al. The potential roles of EZH2 in regenerative medicine［J］. Cell Transplant, 2015, 24(3): 313317. DOI: 10.3727/096368915X686823. ［10］ Zhang J, Ding L, Holmfeldt L, et al. The genetic basis of early Tcell precursor acute lymphoblastic leukaemia［J］. Nature, 2012, 481(7380): 157163. DOI: 10.1038/nature10725. ［11］ Yokoyama Y, Matsumoto A, Hieda M, et al. Loss of histone H4K20 trimethylation predicts poor prognosis in breast cancer and is associated with invasive activity［J］. Breast Cancer Res, 2014, 16(3): R66. DOI: 10.1186/bcr3681. ［12］ Zhao QY, Lei PJ, Zhang X, et al. Global histone modification profiling reveals the epigenomic dynamics during malignant transformation in a fourstage breast cancer model［J］. Clin Epigenetics, 2016, 8: 34. DOI: 10.1186/s131480160201x. ［13］ Healey MA, Hu R, Beck AH, et al. Association of H3K9me3 and H3K27me3 repressive histone marks with breast cancer subtypes in the Nurses′ Health Study［J］. Breast Cancer Res Treat, 2014, 147(3): 639651. DOI: 10.1007/s1054901430891. ［14］ Holm K, Grabau D, Lvgren K, et al. Global H3K27 trimethylation and EZH2 abundance in breast tumor subtypes［J］. Mol Oncol, 2012, 6(5): 494506. DOI: 10.1016/j.molonc.2012.06.002. ［15］ Xu B, Konze KD, Jin J, et al. Targeting EZH2 and PRC2 dependence as novel anticancer therapy［J］. Exp Hematol, 2015, 43(8): 698712. DOI: 10.1016/j.exphem.2015.05.001. ［16］ Dessauvagie BF, Thomas C, Robinson C, et al. Validation of mitosis counting by automated phosphohistone H3 (PHH3) digital image analysis in a breast carcinoma tissue microarray［J］. Pathology, 2015, 47(4): 329334. DOI: 10.1097/PAT.0000000000000248. ［17］ Klintman M, Strand C, Ahlin C, et al. The prognostic value of mitotic activity index (MAI), phosphohistone H3 (PPH3), cyclin B1, cyclin A, and Ki67, alone and in combinations, in nodenegative premenopausal breast cancer［J］. PLoS One, 2013, 8(12): e81902. DOI: 10.1371/journal.pone.0081902. ［18］ Harshman SW, Hoover ME, Huang C, et al. Histone H1 phosphorylation in breast cancer［J］. J Proteome Res, 2014, 13(5): 24532467. DOI: 10.1021/pr401248f. ［19］ Prenzel T, Begusnahrmann Y, Kramer F, et al. Estrogendependent gene transcription in human breast cancer cells relies upon proteasomedependent monoubiquitination of histone H2B［J］. Cancer Res, 2011, 71(17): 57395753. DOI: 10.1158/00085472.CAN111896. ［20］ Cole AJ, CliftonBligh R, Marsh DJ. Histone H2B monoubiquitination: roles to play in human malignancy［J］. Endocr Relat Cancer, 2015, 22(1): T19T33. DOI: 10.1530/ERC140185. ［21］ Dawson MA, Kouzarides T. Cancer epigenetics: from mechanism to therapy［J］. Cell, 2012, 150(1): 1227. DOI: 10.1016/j.cell.2012.06.013. ［22］ Krze′slak A, Forma E, Bernaciak M, et al. Gene expression of OGlcNAc cycling enzymes in human breast cancers［J］. Clin Exp Med, 2012, 12(1): 6165. DOI: 10.1007/s1023801101385. ［23］ Bogachek MV, Chen Y, Kulak MV, et al. Sumoylation pathway is required to maintain the basal breast cancer subtype［J］. Cancer Cell, 2014, 25(6): 748761. DOI: 10.1016/j.ccr.2014.04.008. ［24］ Morera L, Lübbert M, Jung M, et al. Targeting histone methyltransferases and demethylases in clinical trials for cancer therapy［J］. Clin Epigenetics, 2016, 8: 57. DOI: 10.1186/s1314801602234. ［25］ Lakshmaiah KC, Jacob LA, Aparna S, et al. Epigenetic therapy of cancer with histone deacetylase inhibitors［J］. J Cancer Res Ther, 2014, 10(3): 469478. DOI: 10.4103/09731482.137937. ［26］ Huang X, Wang S, Lee CK, et al. HDAC inhibitor SNDX275 enhances efficacy of trastuzumab in erbB2overexpressing breast cancer cells and exhibits potential to overcome trastuzumab resistance［J］. Cancer Lett, 2011, 307(1): 7279. DOI: 10.1016/j.canlet.2011.03.019. ［27］ Huynh KT, Chong KK, Greenberg ES, et al. Epigenetics of estrogen receptornegative primary breast cancer［J］. Expert Rev Mol Diagn, 2012, 12(4): 371382. DOI: 10.1586/erm.12.26. ［28］ Munster PN, Thurn KT, Thomas S, et al. A phase Ⅱ study of the histone deacetylase inhibitor vorinostat combined with tamoxifen for the treatment of patients with hormone therapyresistant breast cancer［J］. Br J Cancer, 2011, 104(12): 18281835. DOI: 10.1038/bjc.2011.156. ［29］ McCabe MT, Ott HM, Ganji G, et al. EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2activating mutations［J］. Nature, 2012, 492(7427): 108112. DOI: 10.1038/nature11606. ［30］ Daigle SR, Olhava EJ, Therkelsen CA, et al. Potent inhibition of DOT1L as treatment of MLLfusion leukemia［J］. Blood, 2013, 122(6): 10171025. DOI: 10.1182/blood201304497644. ［31］ Klaus CR, Iwanowicz D, Johnston D, et al. DOT1L inhibitor EPZ5676 displays synergistic antiproliferative activity in combination with standard of care drugs and hypomethylating agents in MLLrearranged leukemia cells［J］. J Pharmacol Exp Ther, 2014, 350(3): 646645. DOI: 10.1124/jpet.114.214577. ［32］ RodríguezParedes M, Esteller M. Cancer epigenetics reaches mainstream oncology［J］. Nat Med, 2011, 17(3): 330339. DOI: 10.1038/nm.2305. ［33］ Chen CW, Koche RP, Sinha AU, et al. DOT1L inhibits SIRT1mediated epigenetic silencing to maintain leukemic gene expression in MLLrearranged leukemia［J］. Nat Med, 2015, 21(4): 335343. DOI: 10.1038/nm.3832. ［34］ Zagni C, Chiacchio U, Rescifina A. Histone methyltransferase inhibitors: novel epigenetic agents for cancer treatment［J］. Curr Med Chem, 2013, 20(2): 167185. ［35］ Kim TD, Shin S, Berry WL, et al. The JMJD2A demethylase regulates apoptosis and proliferation in colon cancer cells［J］. J Cell Biochem, 2012, 113(4): 13681376. DOI: 10.1002/jcb.24009. ［36］ Kogure M, Takawa M, Cho HS, et al. Deregulation of the histone demethylase JMJD2A is involved in human carcinogenesis through regulation of the G(1)/S transition［J］. Cancer Lett, 2013, 336(1): 7684. DOI: 10.1016/j.canlet.2013.04.009. ［37］ Berry WL, Shin S, Lightfoot SA, et al. Oncogenic features of the JMJD2A histone demethylase in breast cancer［J］. Int J Oncol, 2012, 41(5): 17011706. DOI: 10.3892/ijo.2012.1618. ［38］ Lim S, Janzer A, Becker A, et al. Lysinespecific demethylase 1 (LSD1) is highly expressed in ERnegative breast cancers and a biomarker predicting aggressive biology［J］. Carcinogenesis, 2010, 31(3): 512520. DOI: 10.1093/carcin/bgp324.

[1]	王盈, 刘楠, 郭兵. 抗体药物偶联物在转移性乳腺癌治疗中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 364-369.
[2]	萨蔷, 徐航程, 王佳玉. 乳腺癌免疫治疗研究进展[J]. 国际肿瘤学杂志, 2024, 51(4): 227-234.
[3]	杨智, 陆以乔, 顾花艳, 丁佳玲, 郭贵龙. 肿瘤微环境介导乳腺癌靶向治疗耐药的研究进展[J]. 国际肿瘤学杂志, 2024, 51(4): 235-238.
[4]	陈波光, 王苏贵, 张永杰. 血清胆碱酯酶与炎症标志物在ⅠA~ⅢA期乳腺癌预后中的作用[J]. 国际肿瘤学杂志, 2024, 51(2): 73-82.
[5]	顾花艳, 朱腾, 郭贵龙. 乳房微生物群与乳腺癌：现状与未来[J]. 国际肿瘤学杂志, 2024, 51(1): 55-58.
[6]	王景, 许文婷. 中性粒细胞与淋巴细胞比值、癌胚抗原联合凝血指标对直径≤1.0 cm的良恶性乳腺结节鉴别诊断价值研究[J]. 国际肿瘤学杂志, 2023, 50(9): 520-526.
[7]	冯诚天, 黄芙蓉, 曹世玉, 王健宇, 南丁阿比雅思, 姜永冬, 朱娟英. HER2阳性乳腺癌患者HER2表达水平与影像学特征的关系[J]. 国际肿瘤学杂志, 2023, 50(9): 527-531.
[8]	冯东旭, 吴炜, 高平发, 王军, 施丽娟, 陈大伟, 李文兵, 张美峰. miR-451通过调控Rho/ROCK1信号通路对乳腺癌细胞糖酵解及凋亡的影响[J]. 国际肿瘤学杂志, 2023, 50(8): 449-456.
[9]	王文德, 曾德. 乳腺癌内分泌治疗耐药的机制研究进展[J]. 国际肿瘤学杂志, 2023, 50(6): 352-356.
[10]	李青珊, 谢鑫, 张楠, 刘帅. 放疗联合系统治疗在乳腺癌中的应用进展[J]. 国际肿瘤学杂志, 2023, 50(6): 362-367.
[11]	朱军, 黄美金, 李媛, 刘泽刚, 荀欣, 陈宏. HER2低表达乳腺癌的靶向治疗研究进展[J]. 国际肿瘤学杂志, 2023, 50(4): 236-240.
[12]	周婷, 徐少华, 梅林. 贝伐珠单抗联合卡培他滨治疗晚期乳腺癌的有效性及安全性[J]. 国际肿瘤学杂志, 2023, 50(3): 144-149.
[13]	黎立喜, 张娣, 罗扬, 马飞. PARP抑制剂在乳腺癌中的临床应用[J]. 国际肿瘤学杂志, 2023, 50(2): 91-96.
[14]	陈群响, 张晓钰, 张妍, 张凯翔, 李捷, 陈曦. 伊尼妥单抗联合长春瑞滨治疗HER2阳性转移性乳腺癌1例[J]. 国际肿瘤学杂志, 2023, 50(12): 763-765.
[15]	耿睿, 马俊强, 郭强, 牛钊峰. 老年乳腺癌患者的综合治疗方式选择倾向及其影响因素[J]. 国际肿瘤学杂志, 2023, 50(11): 650-654.