Targeting the Epigenome as a Novel Therapeutic Approach for Breast Cancer

  • Sumin Oh
  • Je Yeong Ko
  • Chaeun Oh
  • Kyung Hyun YooEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1026)


Breast cancer is one of complex diseases that are influenced by environment. Various genetic and epigenetic alterations are provoking causes of breast carcinogenesis. Dynamic epigenetic regulation including DNA methylation and histone modification induces dysregulation of genes related to proliferation, apoptosis, and metastasis in breast cancer. DNA methylation is strongly associated with the repression of transcription through adding to the methyl group by DNA methyltransferases (DNMTs), and tumor suppressor genes such as CCND2 and RUNX3 have been investigated to undergo hypermethylation at promoter region in breast cancer. In addition, histone deacetylases (HDACs) contribute to transcriptional repression by removing acetyl group at lysine residues leading to tumorigenesis. Since epigenetic changes are reversible, therapeutic approaches have been applied with epigenetic modification drugs such as DNMT inhibitors and HDAC inhibitors. In this chapter, we will summarize the feature of epigenetic markers in breast cancer cells and the effect of single or combination of epigenetic reagents for breast cancer therapy.


Epigenetic regulation DNMT inhibitors HDAC inhibitors Therapeutic targets Breast cancer 


  1. 1.
    Dai X, Xiang L, Li T, Bai Z (2016) Cancer hallmarks, biomarkers and breast cancer molecular subtypes. J Cancer 7(10):1281–1294. doi: 10.7150/jca.13141 PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Schnitt SJ (2010) Classification and prognosis of invasive breast cancer: from morphology to molecular taxonomy. Mod Pathol 23(Suppl 2):S60–S64. doi: 10.1038/modpathol.2010.33
  3. 3.
    Weitzel JN, Lagos VI, Cullinane CA, Gambol PJ, Culver JO, Blazer KR, Palomares MR, Lowstuter KJ, MacDonald DJ (2007) Limited family structure and BRCA gene mutation status in single cases of breast cancer. JAMA 297(23):2587–2595. doi: 10.1001/jama.297.23.2587 PubMedCrossRefGoogle Scholar
  4. 4.
    Ferrone CR, Levine DA, Tang LH, Allen PJ, Jarnagin W, Brennan MF, Offit K, Robson ME (2009) BRCA germline mutations in Jewish patients with pancreatic adenocarcinoma. J Clin Oncol 27(3):433–438. doi: 10.1200/JCO.2008.18.5546 PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Chen S, Parmigiani G (2007) Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 25(11):1329–1333. doi: 10.1200/JCO.2006.09.1066 PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Tai YC, Domchek S, Parmigiani G, Chen S (2007) Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst 99(23):1811–1814. doi: 10.1093/jnci/djm203 PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, Loman N, Olsson H, Johannsson O, Borg A, Pasini B, Radice P, Manoukian S, Eccles DM, Tang N, Olah E, Anton-Culver H, Warner E, Lubinski J, Gronwald J, Gorski B, Tulinius H, Thorlacius S, Eerola H, Nevanlinna H, Syrjakoski K, Kallioniemi OP, Thompson D, Evans C, Peto J, Lalloo F, Evans DG, Easton DF (2003) Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 72(5):1117–1130. doi: 10.1086/375033 PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Archey WB, Arrick BA (2017) Transactivation of the estrogen receptor promoter by BRCA1. Cancer Cell Int 17:33. doi: 10.1186/s12935-017-0401-2 PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Li Q, Wei W, Jiang YI, Yang H, Liu J (2015) Promoter methylation and expression changes of BRCA1 in cancerous tissues of patients with sporadic breast cancer. Oncol Lett 9(4):1807–1813. doi: 10.3892/ol.2015.2908 PubMedPubMedCentralGoogle Scholar
  10. 10.
    Al-Moghrabi N, Nofel A, Al-Yousef N, Madkhali S, Bin Amer SM, Alaiya A, Shinwari Z, Al-Tweigeri T, Karakas B, Tulbah A, Aboussekhra A (2014) The molecular significance of methylated BRCA1 promoter in white blood cells of cancer-free females. BMC Cancer 14:830. doi: 10.1186/1471-2407-14-830 PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Rice JC, Ozcelik H, Maxeiner P, Andrulis I, Futscher BW (2000) Methylation of the BRCA1 promoter is associated with decreased BRCA1 mRNA levels in clinical breast cancer specimens. Carcinogenesis 21(9):1761–1765PubMedCrossRefGoogle Scholar
  12. 12.
    Hsu NC, Huang YF, Yokoyama KK, Chu PY, Chen FM, Hou MF (2013) Methylation of BRCA1 promoter region is associated with unfavorable prognosis in women with early-stage breast cancer. PLoS One 8(2):e56256. doi: 10.1371/journal.pone.0056256 PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Jing F, Zhang J, Tao J, Zhou Y, Jun L, Tang X, Wang Y, Hai H (2007) Hypermethylation of tumor suppressor genes BRCA1, p16 and 14-3-3sigma in serum of sporadic breast cancer patients. Onkologie 30(1–2):14–19. doi: 10.1159/000096892 PubMedGoogle Scholar
  14. 14.
    Birgisdottir V, Stefansson OA, Bodvarsdottir SK, Hilmarsdottir H, Jonasson JG, Eyfjord JE (2006) Epigenetic silencing and deletion of the BRCA1 gene in sporadic breast cancer. Breast Cancer Res 8(4):R38. doi: 10.1186/bcr1522 PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Otani Y, Miyake T, Kagara N, Shimoda M, Naoi Y, Maruyama N, Shimomura A, Shimazu K, Kim SJ, Noguchi S (2014) BRCA1 promoter methylation of normal breast epithelial cells as a possible precursor for BRCA1-methylated breast cancer. Cancer Sci 105(10):1369–1376. doi: 10.1111/cas.12506 PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Snell C, Krypuy M, Wong EM, kConFab investigators, Loughrey MB, Dobrovic A (2008) BRCA1 promoter methylation in peripheral blood DNA of mutation negative familial breast cancer patients with a BRCA1 tumour phenotype. Breast Cancer Res 10(1):R12. doi: 10.1186/bcr1858 PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Niwa Y, Oyama T, Nakajima T (2000) BRCA1 expression status in relation to DNA methylation of the BRCA1 promoter region in sporadic breast cancers. Jpn J Cancer Res 91(5):519–526PubMedCrossRefGoogle Scholar
  18. 18.
    Pirouzpanah S, Taleban FA, Mehdipour P, Atri M (2015) Association of folate and other one-carbon related nutrients with hypermethylation status and expression of RARB, BRCA1, and RASSF1A genes in breast cancer patients. J Mol Med (Berl) 93(8):917–934. doi: 10.1007/s00109-015-1268-0 CrossRefGoogle Scholar
  19. 19.
    Zhang L, Long X (2015) Association of BRCA1 promoter methylation with sporadic breast cancers: evidence from 40 studies. Sci Rep 5:17869. doi: 10.1038/srep17869 PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Fucito A, Lucchetti C, Giordano A, Romano G (2008) Genetic and epigenetic alterations in breast cancer: what are the perspectives for clinical practice? Int J Biochem Cell Biol 40(4):565–575. doi: 10.1016/j.biocel.2007.10.018 PubMedCrossRefGoogle Scholar
  21. 21.
    Lo PK, Sukumar S (2008) Epigenomics and breast cancer. Pharmacogenomics 9(12):1879–1902. doi: 10.2217/14622416.9.12.1879 PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Dworkin AM, Huang TH, Toland AE (2009) Epigenetic alterations in the breast: implications for breast cancer detection, prognosis and treatment. Semin Cancer Biol 19(3):165–171. doi: 10.1016/j.semcancer.2009.02.007 PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Jovanovic J, Ronneberg JA, Tost J, Kristensen V (2010) The epigenetics of breast cancer. Mol Oncol 4(3):242–254. doi: 10.1016/j.molonc.2010.04.002 PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Byler S, Goldgar S, Heerboth S, Leary M, Housman G, Moulton K, Sarkar S (2014) Genetic and epigenetic aspects of breast cancer progression and therapy. Anticancer Res 34(3):1071–1077PubMedGoogle Scholar
  25. 25.
    Karsli-Ceppioglu S, Dagdemir A, Judes G, Ngollo M, Penault-Llorca F, Pajon A, Bignon YJ, Bernard-Gallon D (2014) Epigenetic mechanisms of breast cancer: an update of the current knowledge. Epigenomics 6(6):651–664. doi: 10.2217/epi.14.59 PubMedCrossRefGoogle Scholar
  26. 26.
    Basse C, Arock M (2015) The increasing roles of epigenetics in breast cancer: implications for pathogenicity, biomarkers, prevention and treatment. Int J Cancer 137(12):2785–2794. doi: 10.1002/ijc.29347 PubMedCrossRefGoogle Scholar
  27. 27.
    Shen H, Xu W, Guo R, Rong B, Gu L, Wang Z, He C, Zheng L, Hu X, Hu Z, Shao ZM, Yang P, Wu F, Shi YG, Shi Y, Lan F (2016) Suppression of enhancer Overactivation by a RACK7-histone demethylase complex. Cell 165(2):331–342. doi: 10.1016/j.cell.2016.02.064 PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Leroy G, Dimaggio PA, Chan EY, Zee BM, Blanco MA, Bryant B, Flaniken IZ, Liu S, Kang Y, Trojer P, Garcia BA (2013) A quantitative atlas of histone modification signatures from human cancer cells. Epigenetics Chromatin 6(1):20. doi: 10.1186/1756-8935-6-20 PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    McCullough LE, Chen J, Cho YH, Khankari NK, Bradshaw PT, White AJ, Teitelbaum SL, Terry MB, Neugut AI, Hibshoosh H, Santella RM, Gammon MD (2017) Modification of the association between recreational physical activity and survival after breast cancer by promoter methylation in breast cancer-related genes. Breast Cancer Res 19(1):19. doi: 10.1186/s13058-017-0811-z PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Messier TL, Gordon JA, Boyd JR, Tye CE, Browne G, Stein JL, Lian JB, Stein GS (2016) Histone H3 lysine 4 acetylation and methylation dynamics define breast cancer subtypes. Oncotarget 7(5):5094–5109. doi:10.18632/oncotarget.6922
  31. 31.
    Monteiro FL, Vitorino R, Wang J, Cardoso H, Laranjeira H, Simoes J, Caldas M, Henrique R, Amado F, Williams C, Jeronimo C, Helguero LA (2017) The histone H2A isoform Hist2h2ac is a novel regulator of proliferation and epithelial-mesenchymal transition in mammary epithelial and in breast cancer cells. Cancer Lett 396:42–52. doi: 10.1016/j.canlet.2017.03.007 PubMedCrossRefGoogle Scholar
  32. 32.
    Damaskos C, Valsami S, Kontos M, Spartalis E, Kalampokas T, Kalampokas E, Athanasiou A, Moris D, Daskalopoulou A, Davakis S, Tsourouflis G, Kontzoglou K, Perrea D, Nikiteas N, Dimitroulis D (2017) Histone deacetylase inhibitors: an attractive therapeutic strategy against breast cancer. Anticancer Res 37(1):35–46. doi:10.21873/anticanres.11286
  33. 33.
    Zhao QY, Lei PJ, Zhang X, Zheng JY, Wang HY, Zhao J, Li YM, Ye M, Li L, Wei G, Wu M (2016) Global histone modification profiling reveals the epigenomic dynamics during malignant transformation in a four-stage breast cancer model. Clin Epigenetics 8:34. doi: 10.1186/s13148-016-0201-x PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Huang Y, Nayak S, Jankowitz R, Davidson NE, Oesterreich S (2011) Epigenetics in breast cancer: what's new? Breast Cancer Res 13(6):225. doi: 10.1186/bcr2925 PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Atalay C (2013) Epigenetics in breast cancer. Exp Oncol 35(4):246–249PubMedGoogle Scholar
  36. 36.
    Connolly R, Stearns V (2012) Epigenetics as a therapeutic target in breast cancer. J Mammary Gland Biol Neoplasia 17(3–4):191–204. doi: 10.1007/s10911-012-9263-3 PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Vo AT, Millis RM (2012) Epigenetics and breast cancers. Obstet Gynecol Int 2012:602720. doi: 10.1155/2012/602720 PubMedPubMedCentralGoogle Scholar
  38. 38.
    Lustberg MB, Ramaswamy B (2011) Epigenetic therapy in breast cancer. Curr Breast Cancer Rep 3(1):34–43. doi: 10.1007/s12609-010-0034-0 PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Lustberg MB, Ramaswamy B (2009) Epigenetic targeting in breast cancer: therapeutic impact and future direction. Drug News Perspect 22(7):369–381. doi: 10.1358/dnp.2009.22.7.1405072 PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Ai L, Kim WJ, Kim TY, Fields CR, Massoll NA, Robertson KD, Brown KD (2006) Epigenetic silencing of the tumor suppressor cystatin M occurs during breast cancer progression. Cancer Res 66(16):7899–7909. doi: 10.1158/0008-5472.CAN-06-0576 PubMedCrossRefGoogle Scholar
  41. 41.
    Boyanapalli SS, Li W, Fuentes F, Guo Y, Ramirez CN, Gonzalez XP, Pung D, Kong AN (2016) Epigenetic reactivation of RASSF1A by phenethyl isothiocyanate (PEITC) and promotion of apoptosis in LNCaP cells. Pharmacol Res 114:175–184. doi: 10.1016/j.phrs.2016.10.021 PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Sinha S, Shukla S, Khan S, Tollefsbol TO, Meeran SM (2015) Epigenetic reactivation of p21CIP1/WAF1 and KLOTHO by a combination of bioactive dietary supplements is partially ERalpha-dependent in ERalpha-negative human breast cancer cells. Mol Cell Endocrinol 406:102–114. doi: 10.1016/j.mce.2015.02.020 PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Klarmann GJ, Decker A, Farrar WL (2008) Epigenetic gene silencing in the Wnt pathway in breast cancer. Epigenetics 3(2):59–63PubMedCrossRefGoogle Scholar
  44. 44.
    Perri F, Longo F, Giuliano M, Sabbatino F, Favia G, Ionna F, Addeo R, Della Vittoria Scarpati G, Di Lorenzo G, Pisconti S (2017) Epigenetic control of gene expression: potential implications for cancer treatment. Crit Rev Oncol Hematol 111:166–172. doi: 10.1016/j.critrevonc.2017.01.020 PubMedCrossRefGoogle Scholar
  45. 45.
    Connolly RM, Rudek MA, Piekarz R (2017) Entinostat: a promising treatment option for patients with advanced breast cancer. Future Oncol. doi: 10.2217/fon-2016-0526
  46. 46.
    Deb M, Sengupta D, Kar S, Rath SK, Parbin S, Shilpi A, Roy S, Das G, Patra SK (2014) Elucidation of caveolin 1 both as a tumor suppressor and metastasis promoter in light of epigenetic modulators. Tumour Biol 35(12):12031–12047. doi: 10.1007/s13277-014-2502-z PubMedCrossRefGoogle Scholar
  47. 47.
    Ambatipudi S, Horvath S, Perrier F, Cuenin C, Hernandez-Vargas H, Le Calvez-Kelm F, Durand G, Byrnes G, Ferrari P, Bouaoun L, Sklias A, Chajes V, Overvad K, Severi G, Baglietto L, Clavel-Chapelon F, Kaaks R, Barrdahl M, Boeing H, Trichopoulou A, Lagiou P, Naska A, Masala G, Agnoli C, Polidoro S, Tumino R, Panico S, Dolle M, Peeters PH, Onland-Moret NC, Sandanger TM, Nost TH, Weiderpass E, Quiros JR, Agudo A, Rodriguez-Barranco M, Huerta Castano JM, Barricarte A, Fernandez AM, Travis RC, Vineis P, Muller DC, Riboli E, Gunter M, Romieu I, Herceg Z (2017) DNA methylome analysis identifies accelerated epigenetic ageing associated with postmenopausal breast cancer susceptibility. Eur J Cancer 75:299–307. doi: 10.1016/j.ejca.2017.01.014 PubMedCrossRefGoogle Scholar
  48. 48.
    Longacre M, Snyder NA, Housman G, Leary M, Lapinska K, Heerboth S, Willbanks A, Sarkar S (2016) A comparative analysis of genetic and epigenetic events of breast and ovarian cancer related to tumorigenesis. Int J Mol Sci 17(5). doi: 10.3390/ijms17050759
  49. 49.
    Schubeler D (2015) Function and information content of DNA methylation. Nature 517(7534):321–326. doi: 10.1038/nature14192 PubMedCrossRefGoogle Scholar
  50. 50.
    Jin B, Li Y, Robertson KD (2011) DNA methylation: superior or subordinate in the epigenetic hierarchy? Genes Cancer 2(6):607–617. doi: 10.1177/1947601910393957 PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Cheng X, Blumenthal RM (2008) Mammalian DNA methyltransferases: a structural perspective. Structure 16(3):341–350. doi: 10.1016/j.str.2008.01.004 PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Okano M, Xie S, Li E (1998) Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nat Genet 19(3):219–220. doi: 10.1038/890 PubMedCrossRefGoogle Scholar
  53. 53.
    Bestor TH (2000) The DNA methyltransferases of mammals. Hum Mol Genet 9(16):2395–2402PubMedCrossRefGoogle Scholar
  54. 54.
    Szyf M (2012) DNA methylation signatures for breast cancer classification and prognosis. Genome Med 4(3):26. doi: 10.1186/gm325 PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Martens JW, Margossian AL, Schmitt M, Foekens J, Harbeck N (2009) DNA methylation as a biomarker in breast cancer. Future Oncol 5(8):1245–1256. doi: 10.2217/fon.09.89 PubMedCrossRefGoogle Scholar
  56. 56.
    Brooks J, Cairns P, Zeleniuch-Jacquotte A (2009) Promoter methylation and the detection of breast cancer. Cancer Causes Control 20(9):1539–1550. doi: 10.1007/s10552-009-9415-y PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Sterner DE, Berger SL (2000) Acetylation of histones and transcription-related factors. Microbiol Mol Biol Rev 64(2):435–459PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Bannister AJ, Kouzarides T (2011) Regulation of chromatin by histone modifications. Cell Res 21(3):381–395. doi: 10.1038/cr.2011.22 PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Chervona Y, Arita A, Costa M (2012) Carcinogenic metals and the epigenome: understanding the effect of nickel, arsenic, and chromium. Metallomics 4(7):619–627. doi: 10.1039/c2mt20033c PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Lawrence M, Daujat S, Schneider R (2016) Lateral thinking: how histone modifications regulate gene expression. Trends Genet 32(1):42–56. doi: 10.1016/j.tig.2015.10.007 PubMedCrossRefGoogle Scholar
  61. 61.
    Dokmanovic M, Clarke C, Marks PA (2007) Histone deacetylase inhibitors: overview and perspectives. Mol Cancer Res 5(10):981–989. doi: 10.1158/1541-7786.MCR-07-0324 PubMedCrossRefGoogle Scholar
  62. 62.
    Marks PA, Xu WS (2009) Histone deacetylase inhibitors: potential in cancer therapy. J Cell Biochem 107(4):600–608. doi: 10.1002/jcb.22185 PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Yang XJ, Seto E (2008) The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men. Nat Rev Mol Cell Biol 9(3):206–218. doi: 10.1038/nrm2346 PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Longworth MS, Laimins LA (2006) Histone deacetylase 3 localizes to the plasma membrane and is a substrate of Src. Oncogene 25(32):4495–4500. doi: 10.1038/sj.onc.1209473 PubMedCrossRefGoogle Scholar
  65. 65.
    Valenzuela-Fernandez A, Cabrero JR, Serrador JM, Sanchez-Madrid F (2008) HDAC6: a key regulator of cytoskeleton, cell migration and cell-cell interactions. Trends Cell Biol 18(6):291–297. doi: 10.1016/j.tcb.2008.04.003 PubMedCrossRefGoogle Scholar
  66. 66.
    Truong PK, Lao TD, Doan TP, Le TA (2015) Loss of expression of cyclin d2 by aberrant DNA methylation: a potential biomarker in vietnamese breast cancer patients. Asian Pac J Cancer Prev 16(6):2209–2213PubMedCrossRefGoogle Scholar
  67. 67.
    Lewis CM, Cler LR, Bu DW, Zochbauer-Muller S, Milchgrub S, Naftalis EZ, Leitch AM, Minna JD, Euhus DM (2005) Promoter hypermethylation in benign breast epithelium in relation to predicted breast cancer risk. Clin Cancer Res 11(1):166–172PubMedGoogle Scholar
  68. 68.
    Ramezani F, Salami S, Omrani MD, Maleki D (2012) CpG island methylation profile of estrogen receptor alpha in Iranian females with triple negative or non-triple negative breast cancer: new marker of poor prognosis. Asian Pac J Cancer Prev 13(2):451–457PubMedCrossRefGoogle Scholar
  69. 69.
    Maekawa R, Sato S, Okada M, Lee L, Tamura I, Jozaki K, Kajimura T, Asada H, Yamagata Y, Tamura H, Yamamoto S, Sugino N (2016) Tissue-specific expression of estrogen receptor 1 is regulated by DNA methylation in a T-DMR. Mol Endocrinol 30(3):335–347. doi: 10.1210/me.2015-1058 PubMedCrossRefGoogle Scholar
  70. 70.
    Gao L, Qi X, Hu K, Zhu R, Xu W, Sun S, Zhang L, Yang X, Hua B, Liu G (2016) Estrogen receptor beta promoter methylation: a potential indicator of malignant changes in breast cancer. Arch Med Sci 12(1):129–136. doi: 10.5114/aoms.2016.57588 PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Zhang W, Chang Z, Shi KE, Song L, Cui LI, Ma Z, Li X, Ma W, Wang L (2016) The correlation between DNMT1 and ERalpha expression and the methylation status of ERalpha, and its clinical significance in breast cancer. Oncol Lett 11(3):1995–2000. doi: 10.3892/ol.2016.4193 PubMedPubMedCentralGoogle Scholar
  72. 72.
    Dewi DL, Mohapatra SR, Blanco Cabanes S, Adam I, Somarribas Patterson LF, Berdel B, Kahloon M, Thurmann L, Loth S, Heilmann K, Weichenhan D, Mucke O, Heiland I, Wimberger P, Kuhlmann JD, Kellner KH, Schott S, Plass C, Platten M, Gerhauser C, Trump S, Opitz CA (2017) Suppression of indoleamine-2,3-dioxygenase 1 expression by promoter hypermethylation in ER-positive breast cancer. Oncoimmunology 6(2):e1274477. doi: 10.1080/2162402X.2016.1274477 PubMedCrossRefGoogle Scholar
  73. 73.
    Mao X, Qiao Z, Fan C, Guo A, Yu X, Jin F (2016) Expression pattern and methylation of estrogen receptor alpha in breast intraductal proliferative lesions. Oncol Rep 36(4):1868–1874. doi: 10.3892/or.2016.4988 PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Piva R, Rimondi AP, Hanau S, Maestri I, Alvisi A, Kumar VL, del Senno L (1990) Different methylation of oestrogen receptor DNA in human breast carcinomas with and without oestrogen receptor. Br J Cancer 61(2):270–275PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Hori M, Iwasaki M, Yoshimi F, Asato Y, Itabashi M (1999) Hypermethylation of the estrogen receptor alpha gene is not related to lack of receptor protein in human breast cancer. Breast Cancer 6(2):79–86PubMedCrossRefGoogle Scholar
  76. 76.
    Medina-Jaime AD, Reyes-Vargas F, Martinez-Gaytan V, Zambrano-Galvan G, Portillo-Delcampo E, Burciaga-Nava JA, Reyes-Romero M, Sifuentes-Alvarez A (2014) ESR1 and PGR gene promoter methylation and correlations with estrogen and progesterone receptors in ductal and lobular breast cancer. Asian Pac J Cancer Prev 15(7):3041–3044PubMedCrossRefGoogle Scholar
  77. 77.
    Gaudet MM, Campan M, Figueroa JD, Yang XR, Lissowska J, Peplonska B, Brinton LA, Rimm DL, Laird PW, Garcia-Closas M, Sherman ME (2009) DNA hypermethylation of ESR1 and PGR in breast cancer: pathologic and epidemiologic associations. Cancer Epidemiol Biomark Prev 18(11):3036–3043. doi: 10.1158/1055-9965.EPI-09-0678 CrossRefGoogle Scholar
  78. 78.
    Jiang Y, Tong D, Lou G, Zhang Y, Geng J (2008) Expression of RUNX3 gene, methylation status and clinicopathological significance in breast cancer and breast cancer cell lines. Pathobiology 75(4):244–251. doi: 10.1159/000132385 PubMedCrossRefGoogle Scholar
  79. 79.
    Lu DG, Ma YM, Zhu AJ, Han YW (2016) An early biomarker and potential therapeutic target of RUNX 3 hypermethylation in breast cancer, a system review and meta-analysis. Oncotarget. doi:10.18632/oncotarget.13125
  80. 80.
    Song XY, Li BY, Zhou EX, Wu FX (2016) The clinicopathological significance of RUNX3 hypermethylation and mRNA expression in human breast cancer, a meta-analysis. Onco Targets Ther 9:5339–5347. doi: 10.2147/OTT.S77828 PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Yu YY, Chen C, Kong FF, Zhang W (2014) Clinicopathological significance and potential drug target of RUNX3 in breast cancer. Drug Des Devel Ther 8:2423–2430. doi: 10.2147/DDDT.S71815 PubMedPubMedCentralGoogle Scholar
  82. 82.
    Kang HF, Dai ZJ, Bai HP, Lu WF, Ma XB, Bao X, Lin S, Wang XJ (2013) RUNX3 gene promoter demethylation by 5-Aza-CdR induces apoptosis in breast cancer MCF-7 cell line. Onco Targets Ther 6:411–417. doi: 10.2147/OTT.S43744 PubMedPubMedCentralGoogle Scholar
  83. 83.
    Subramaniam MM, Chan JY, Omar MF, Ito K, Ito Y, Yeoh KG, Salto-Tellez M, Putti TC (2010) Lack of RUNX3 inactivation in columnar cell lesions of breast. Histopathology 57(4):555–563. doi: 10.1111/j.1365-2559.2010.03675.x PubMedCrossRefGoogle Scholar
  84. 84.
    Subramaniam MM, Chan JY, Soong R, Ito K, Ito Y, Yeoh KG, Salto-Tellez M, Putti TC (2009) RUNX3 inactivation by frequent promoter hypermethylation and protein mislocalization constitute an early event in breast cancer progression. Breast Cancer Res Treat 113(1):113–121. doi: 10.1007/s10549-008-9917-4 PubMedCrossRefGoogle Scholar
  85. 85.
    Hwang KT, Han W, Bae JY, Hwang SE, Shin HJ, Lee JE, Kim SW, Min HJ, Noh DY (2007) Downregulation of the RUNX3 gene by promoter hypermethylation and hemizygous deletion in breast cancer. J Korean Med Sci 22(Suppl):S24–S31. doi: 10.3346/jkms.2007.22.S.S24 PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Li Y, Melnikov AA, Levenson V, Guerra E, Simeone P, Alberti S, Deng Y (2015) A seven-gene CpG-island methylation panel predicts breast cancer progression. BMC Cancer 15:417. doi: 10.1186/s12885-015-1412-9 PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Cho YH, McCullough LE, Gammon MD, Wu HC, Zhang YJ, Wang Q, Xu X, Teitelbaum SL, Neugut AI, Chen J, Santella RM (2015) Promoter Hypermethylation in white blood cell DNA and breast cancer risk. J Cancer 6(9):819–824. doi: 10.7150/jca.12174 PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Chen ST, Lin SY, Yeh KT, Kuo SJ, Chan WL, Chu YP, Chang JG (2004) Mutational, epigenetic and expressional analyses of caveolin-1 gene in breast cancers. Int J Mol Med 14(4):577–582PubMedGoogle Scholar
  89. 89.
    Hong CP, Choe MK, Roh TY (2012) Characterization of chromatin structure-associated histone modifications in breast cancer cells. Genomics Inform 10(3):145–152. doi: 10.5808/GI.2012.10.3.145 PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Costello JF, Fruhwald MC, Smiraglia DJ, Rush LJ, Robertson GP, Gao X, Wright FA, Feramisco JD, Peltomaki P, Lang JC, Schuller DE, Yu L, Bloomfield CD, Caligiuri MA, Yates A, Nishikawa R, Su Huang H, Petrelli NJ, Zhang X, O'Dorisio MS, Held WA, Cavenee WK, Plass C (2000) Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. Nat Genet 24(2):132–138. doi: 10.1038/72785 PubMedCrossRefGoogle Scholar
  91. 91.
    Esteller M (2007) Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet 8(4):286–298. doi: 10.1038/nrg2005 PubMedCrossRefGoogle Scholar
  92. 92.
    Lo PK, Mehrotra J, D'Costa A, Fackler MJ, Garrett-Mayer E, Argani P, Sukumar S (2006) Epigenetic suppression of secreted frizzled related protein 1 (SFRP1) expression in human breast cancer. Cancer Biol Ther 5(3):281–286PubMedCrossRefGoogle Scholar
  93. 93.
    Dagdemir A, Judes G, Lebert A, Echegut M, Karsli-Ceppioglu S, Rifai K, Daures M, Ngollo M, Dubois L, Penault-Llorca F, Bignon YJ, Bernard-Gallon D (2016) Epigenetic modifications with DZNep, NaBu and SAHA in luminal and mesenchymal-like breast cancer subtype cells. Cancer Genomics Proteomics 13(4):291–303PubMedGoogle Scholar
  94. 94.
    Agathanggelou A, Dallol A, Zochbauer-Muller S, Morrissey C, Honorio S, Hesson L, Martinsson T, Fong KM, Kuo MJ, Yuen PW, Maher ER, Minna JD, Latif F (2003) Epigenetic inactivation of the candidate 3p21.3 suppressor gene BLU in human cancers. Oncogene 22(10):1580–1588. doi: 10.1038/sj.onc.1206243 PubMedCrossRefGoogle Scholar
  95. 95.
    Asiaf A, Ahmad ST, Aziz SA, Malik AA, Rasool Z, Masood A, Zargar MA (2014) Loss of expression and aberrant methylation of the CDH1 (E-cadherin) gene in breast cancer patients from Kashmir. Asian Pac J Cancer Prev 15(15):6397–6403PubMedCrossRefGoogle Scholar
  96. 96.
    Alvarez C, Tapia T, Cornejo V, Fernandez W, Munoz A, Camus M, Alvarez M, Devoto L, Carvallo P (2013) Silencing of tumor suppressor genes RASSF1A, SLIT2, and WIF1 by promoter hypermethylation in hereditary breast cancer. Mol Carcinog 52(6):475–487. doi: 10.1002/mc.21881 PubMedCrossRefGoogle Scholar
  97. 97.
    Askari M, Sobti RC, Nikbakht M, Sharma SC (2013) Promoter hypermethylation of tumour suppressor genes (p14/ARF and p16/INK4a): case-control study in north Indian population. Mol Biol Rep 40(8):4921–4928. doi: 10.1007/s11033-013-2592-5 PubMedCrossRefGoogle Scholar
  98. 98.
    Bachman KE, Herman JG, Corn PG, Merlo A, Costello JF, Cavenee WK, Baylin SB, Graff JR (1999) Methylation-associated silencing of the tissue inhibitor of metalloproteinase-3 gene suggest a suppressor role in kidney, brain, and other human cancers. Cancer Res 59(4):798–802PubMedGoogle Scholar
  99. 99.
    Bae YK, Shim YR, Choi JH, Kim MJ, Gabrielson E, Lee SJ, Hwang TY, Shin SO (2005) Gene promoter hypermethylation in tumors and plasma of breast cancer patients. Cancer Res Treat 37(4):233–240. doi: 10.4143/crt.2005.37.4.233 PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Bagadi SA, Prasad CP, Kaur J, Srivastava A, Prashad R, Gupta SD, Ralhan R (2008) Clinical significance of promoter hypermethylation of RASSF1A, RARbeta2, BRCA1 and HOXA5 in breast cancers of Indian patients. Life Sci 82(25–26):1288–1292. doi: 10.1016/j.lfs.2008.04.020 PubMedCrossRefGoogle Scholar
  101. 101.
    Ballestar E, Paz MF, Valle L, Wei S, Fraga MF, Espada J, Cigudosa JC, Huang TH, Esteller M (2003) Methyl-CpG binding proteins identify novel sites of epigenetic inactivation in human cancer. EMBO J 22(23):6335–6345. doi: 10.1093/emboj/cdg604 PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Boily G, Saikali Z, Sinnett D (2004) Methylation analysis of the glypican 3 gene in embryonal tumours. Br J Cancer 90(8):1606–1611. doi: 10.1038/sj.bjc.6601716 PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Celebiler Cavusoglu A, Sevinc AI, Saydam S, Canda T, Baskan Z, Kilic Y, Sakizli M (2010) Promoter methylation and expression changes of CDH1 and P16 genes in invasive breast cancer and adjacent normal breast tissue. Neoplasma 57(5):465–472PubMedCrossRefGoogle Scholar
  104. 104.
    Chekhun VF, Kulik GI, Yurchenko OV, Tryndyak VP, Todor IN, Luniv LS, Tregubova NA, Pryzimirska TV, Montgomery B, Rusetskaya NV, Pogribny IP (2006) Role of DNA hypomethylation in the development of the resistance to doxorubicin in human MCF-7 breast adenocarcinoma cells. Cancer Lett 231(1):87–93. doi: 10.1016/j.canlet.2005.01.038 PubMedCrossRefGoogle Scholar
  105. 105.
    Chen CM, Chen HL, Hsiau TH, Hsiau AH, Shi H, Brock GJ, Wei SH, Caldwell CW, Yan PS, Huang TH (2003) Methylation target array for rapid analysis of CpG island hypermethylation in multiple tissue genomes. Am J Pathol 163(1):37–45. doi: 10.1016/S0002-9440(10)63628-0 PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Chimonidou M, Tzitzira A, Strati A, Sotiropoulou G, Sfikas C, Malamos N, Georgoulias V, Lianidou E (2013) CST6 promoter methylation in circulating cell-free DNA of breast cancer patients. Clin Biochem 46(3):235–240. doi: 10.1016/j.clinbiochem.2012.09.015 PubMedCrossRefGoogle Scholar
  107. 107.
    Crucianelli F, Tricarico R, Turchetti D, Gorelli G, Gensini F, Sestini R, Giunti L, Pedroni M, Ponz de Leon M, Civitelli S, Genuardi M (2014) MLH1 constitutional and somatic methylation in patients with MLH1 negative tumors fulfilling the revised Bethesda criteria. Epigenetics 9(10):1431–1438. doi: 10.4161/15592294.2014.970080 PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Dallol A, Forgacs E, Martinez A, Sekido Y, Walker R, Kishida T, Rabbitts P, Maher ER, Minna JD, Latif F (2002) Tumour specific promoter region methylation of the human homologue of the drosophila roundabout gene DUTT1 (ROBO1) in human cancers. Oncogene 21(19):3020–3028. doi: 10.1038/sj.onc.1205421 PubMedCrossRefGoogle Scholar
  109. 109.
    Dimitrakopoulos L, Vorkas PA, Georgoulias V, Lianidou ES (2012) A closed-tube methylation-sensitive high resolution melting assay (MS-HRMA) for the semi-quantitative determination of CST6 promoter methylation in clinical samples. BMC Cancer 12:486. doi: 10.1186/1471-2407-12-486 PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Virmani A, Rathi A, Heda S, Sugio K, Lewis C, Tonk V, Takahashi T, Roth JA, Minna JD, Euhus DM, Gazdar AF (2003) Aberrant methylation of the cyclin D2 promoter in primary small cell, nonsmall cell lung and breast cancers. Int J Cancer 107(3):341–345. doi: 10.1002/ijc.11393 PubMedCrossRefGoogle Scholar
  111. 111.
    Virmani A, Rathi A, Sugio K, Sathyanarayana UG, Toyooka S, Kischel FC, Tonk V, Padar A, Takahashi T, Roth JA, Euhus DM, Minna JD, Gazdar AF (2003) Aberrant methylation of TMS1 in small cell, non small cell lung cancer and breast cancer. Int J Cancer 106(2):198–204. doi: 10.1002/ijc.11206 PubMedCrossRefGoogle Scholar
  112. 112.
    Virmani AK, Rathi A, Sathyanarayana UG, Padar A, Huang CX, Cunnigham HT, Farinas AJ, Milchgrub S, Euhus DM, Gilcrease M, Herman J, Minna JD, Gazdar AF (2001) Aberrant methylation of the adenomatous polyposis coli (APC) gene promoter 1A in breast and lung carcinomas. Clin Cancer Res 7(7):1998–2004PubMedGoogle Scholar
  113. 113.
    Wang S, Ding YB, Chen GY, Xia JG, Wu ZY (2004) Hypermethylation of Syk gene in promoter region associated with oncogenesis and metastasis of gastric carcinoma. World J Gastroenterol 10(12):1815–1818PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Wang S, Dorsey TH, Terunuma A, Kittles RA, Ambs S, Kwabi-Addo B (2012) Relationship between tumor DNA methylation status and patient characteristics in African-American and European-American women with breast cancer. PLoS One 7(5):e37928. doi: 10.1371/journal.pone.0037928 PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Weissenborn C, Ignatov T, Nass N, Kalinski T, Dan Costa S, Zenclussen AC, Ignatov A (2017) GPER promoter methylation controls GPER expression in breast cancer patients. Cancer Investig 35(2):100–107. doi: 10.1080/07357907.2016.1271886 CrossRefGoogle Scholar
  116. 116.
    Widschwendter M, Jones PA (2002) DNA methylation and breast carcinogenesis. Oncogene 21(35):5462–5482. doi: 10.1038/sj.onc.1205606 PubMedCrossRefGoogle Scholar
  117. 117.
    Worm J, Kirkin AF, Dzhandzhugazyan KN, Guldberg P (2001) Methylation-dependent silencing of the reduced folate carrier gene in inherently methotrexate-resistant human breast cancer cells. J Biol Chem 276(43):39990–40000. doi: 10.1074/jbc.M103181200 PubMedCrossRefGoogle Scholar
  118. 118.
    Wu HC, Southey MC, Hibshoosh H, Santella RM, Terry MB (2017) DNA methylation in breast tumor from high-risk women in the breast cancer family registry. Anticancer Res 37(2):659–664. doi:10.21873/anticanres.11361
  119. 119.
    Xiang YY, Ladeda V, Filmus J (2001) Glypican-3 expression is silenced in human breast cancer. Oncogene 20(50):7408–7412. doi: 10.1038/sj.onc.1204925 PubMedCrossRefGoogle Scholar
  120. 120.
    Xu J, Shetty PB, Feng W, Chenault C, Bast RC Jr, Issa JP, Hilsenbeck SG, Yu Y (2012) Methylation of HIN-1, RASSF1A, RIL and CDH13 in breast cancer is associated with clinical characteristics, but only RASSF1A methylation is associated with outcome. BMC Cancer 12:243. doi: 10.1186/1471-2407-12-243 PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Yamamoto N, Nakayama T, Kajita M, Miyake T, Iwamoto T, Kim SJ, Sakai A, Ishihara H, Tamaki Y, Noguchi S (2012) Detection of aberrant promoter methylation of GSTP1, RASSF1A, and RARbeta2 in serum DNA of patients with breast cancer by a newly established one-step methylation-specific PCR assay. Breast Cancer Res Treat 132(1):165–173. doi: 10.1007/s10549-011-1575-2 PubMedCrossRefGoogle Scholar
  122. 122.
    Yang J, Niu H, Huang Y, Yang K (2016) A systematic analysis of the relationship of CDH13 promoter methylation and breast cancer risk and prognosis. PLoS One 11(5):e0149185. doi: 10.1371/journal.pone.0149185 PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Yang ZQ, Liu G, Bollig-Fischer A, Haddad R, Tarca AL, Ethier SP (2009) Methylation-associated silencing of SFRP1 with an 8p11-12 amplification inhibits canonical and non-canonical WNT pathways in breast cancers. Int J Cancer 125(7):1613–1621. doi: 10.1002/ijc.24518 PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Yazici H, Terry MB, Cho YH, Senie RT, Liao Y, Andrulis I, Santella RM (2009) Aberrant methylation of RASSF1A in plasma DNA before breast cancer diagnosis in the breast cancer family registry. Cancer Epidemiol Biomark Prev 18(10):2723–2725. doi: 10.1158/1055-9965.EPI-08-1237 CrossRefGoogle Scholar
  125. 125.
    Yeo W, Wong WL, Wong N, Law BK, Tse GM, Zhong S (2005) High frequency of promoter hypermethylation of RASSF1A in tumorous and non-tumourous tissue of breast cancer. Pathology 37(2):125–130PubMedCrossRefGoogle Scholar
  126. 126.
    Yu P, Guo Y, Yusufu M, Liu Z, Wang S, Yin X, Peng G, Wang L, Zhao X, Guo H, Huang T, Liu C (2016) Decreased expression of EZH2 reactivates RASSF2A by reversal of promoter methylation in breast cancer cells. Cell Biol Int 40(10):1062–1070. doi: 10.1002/cbin.10646 PubMedCrossRefGoogle Scholar
  127. 127.
    Zurita M, Lara PC, del Moral R, Torres B, Linares-Fernandez JL, Arrabal SR, Martinez-Galan J, Oliver FJ, Ruiz de Almodovar JM (2010) Hypermethylated 14-3-3-sigma and ESR1 gene promoters in serum as candidate biomarkers for the diagnosis and treatment efficacy of breast cancer metastasis. BMC Cancer 10:217. doi: 10.1186/1471-2407-10-217 PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Zwergel C, Valente S, Mai A (2016) DNA methyltransferases inhibitors from natural sources. Curr Top Med Chem 16(7):680–696PubMedCrossRefGoogle Scholar
  129. 129.
    Elsheikh SE, Green AR, Rakha EA, Powe DG, Ahmed RA, Collins HM, Soria D, Garibaldi JM, Paish CE, Ammar AA, Grainge MJ, Ball GR, Abdelghany MK, Martinez-Pomares L, Heery DM, Ellis IO (2009) Global histone modifications in breast cancer correlate with tumor phenotypes, prognostic factors, and patient outcome. Cancer Res 69(9):3802–3809. doi: 10.1158/0008-5472.CAN-08-3907 PubMedCrossRefGoogle Scholar
  130. 130.
    Dalvai M, Bystricky K (2010) The role of histone modifications and variants in regulating gene expression in breast cancer. J Mammary Gland Biol Neoplasia 15(1):19–33. doi: 10.1007/s10911-010-9167-z PubMedCrossRefGoogle Scholar
  131. 131.
    Yoo KH, Hennighausen L (2012) EZH2 methyltransferase and H3K27 methylation in breast cancer. Int J Biol Sci 8(1):59–65PubMedCrossRefGoogle Scholar
  132. 132.
    Tsai WW, Wang Z, Yiu TT, Akdemir KC, Xia W, Winter S, Tsai CY, Shi X, Schwarzer D, Plunkett W, Aronow B, Gozani O, Fischle W, Hung MC, Patel DJ, Barton MC (2010) TRIM24 links a non-canonical histone signature to breast cancer. Nature 468(7326):927–932. doi: 10.1038/nature09542 PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    Li Y, Li S, Chen J, Shao T, Jiang C, Wang Y, Chen H, Xu J, Li X (2014) Comparative epigenetic analyses reveal distinct patterns of oncogenic pathways activation in breast cancer subtypes. Hum Mol Genet 23(20):5378–5393. doi: 10.1093/hmg/ddu256 PubMedCrossRefGoogle Scholar
  134. 134.
    Droog M, Nevedomskaya E, Dackus GM, Fles R, Kim Y, Hollema H, Mourits M, Nederlof PM, van Boven HH, Linn SC, van Leeuwen FE, Wessels LF, Zwart W (2017) Estrogen receptor alpha wields treatment-specific enhancers between morphologically similar endometrial tumors. Proc Natl Acad Sci U S A 114(8):E1316–E1325. doi: 10.1073/pnas.1615233114 PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Bustos MA, Salomon MP, Nelson N, Hsu SC, DiNome ML, Hoon DS, Marzese DM (2017) Genome-wide chromatin accessibility, DNA methylation and gene expression analysis of histone deacetylase inhibition in triple-negative breast cancer. Genom Data 12:14–16. doi: 10.1016/j.gdata.2017.01.002 PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Connolly RM, Li H, Jankowitz RC, Zhang Z, Rudek MA, Jeter SC, Slater SA, Powers P, Wolff AC, Fetting JH, Brufsky A, Piekarz R, Ahuja N, Laird PW, Shen H, Weisenberger DJ, Cope L, Herman JG, Somlo G, Garcia AA, Jones PA, Baylin SB, Davidson NE, Zahnow CA, Stearns V (2016) Combination epigenetic therapy in advanced breast cancer with 5-Azacitidine and Entinostat: a phase II National Cancer Institute/stand up to cancer study. Clin Cancer Res. doi: 10.1158/1078-0432.CCR-16-1729
  137. 137.
    Oshiro MM, Futscher BW, Lisberg A, Wozniak RJ, Klimecki WT, Domann FE, Cress AE (2005) Epigenetic regulation of the cell type-specific gene 14-3-3sigma. Neoplasia 7(9):799–808PubMedPubMedCentralCrossRefGoogle Scholar
  138. 138.
    Rhie SK, Hazelett DJ, Coetzee SG, Yan C, Noushmehr H, Coetzee GA (2014) Nucleosome positioning and histone modifications define relationships between regulatory elements and nearby gene expression in breast epithelial cells. BMC Genomics 15:331. doi: 10.1186/1471-2164-15-331 PubMedPubMedCentralCrossRefGoogle Scholar
  139. 139.
    Gnyszka A, Jastrzebski Z, Flis S (2013) DNA methyltransferase inhibitors and their emerging role in epigenetic therapy of cancer. Anticancer Res 33(8):2989–2996PubMedGoogle Scholar
  140. 140.
    Girault I, Tozlu S, Lidereau R, Bieche I (2003) Expression analysis of DNA methyltransferases 1, 3A, and 3B in sporadic breast carcinomas. Clin Cancer Res 9(12):4415–4422PubMedGoogle Scholar
  141. 141.
    Manjegowda MC, Gupta PS, Limaye AM (2017) Hyper-methylation of the upstream CpG island shore is a likely mechanism of GPER1 silencing in breast cancer cells. Gene 614:65–73. doi: 10.1016/j.gene.2017.03.006 PubMedCrossRefGoogle Scholar
  142. 142.
    Sadikovic B, Haines TR, Butcher DT, Rodenhiser DI (2004) Chemically induced DNA hypomethylation in breast carcinoma cells detected by the amplification of intermethylated sites. Breast Cancer Res 6(4):R329–R337. doi: 10.1186/bcr799 PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Dong H, Ma L, Gan J, Lin W, Chen C, Yao Z, Du L, Zheng L, Ke C, Huang X, Song H, Kumar R, Yeung SC, Zhang H (2017) PTPRO represses ERBB2-driven breast oncogenesis by dephosphorylation and endosomal internalization of ERBB2. Oncogene 36(3):410–422. doi: 10.1038/onc.2016.213 PubMedCrossRefGoogle Scholar
  144. 144.
    Tao Y, Liu S, Briones V, Geiman TM, Muegge K (2011) Treatment of breast cancer cells with DNA demethylating agents leads to a release of pol II stalling at genes with DNA-hypermethylated regions upstream of TSS. Nucleic Acids Res 39(22):9508–9520. doi: 10.1093/nar/gkr611 PubMedPubMedCentralCrossRefGoogle Scholar
  145. 145.
    Hellreich J, Gasparek J, O'Donnell R (2014) Effects of 5-azacytidine on the in vitro colony growth of the MDA-MB 435 cancer cell line (1047.11). The. FASEB J 28(1 Suppl)Google Scholar
  146. 146.
    Xiang T, Fan Y, Li C, Li L, Ying Y, Mu J, Peng W, Feng Y, Oberst M, Kelly K, Ren G, Tao Q (2016) DACT2 silencing by promoter CpG methylation disrupts its regulation of epithelial-to-mesenchymal transition and cytoskeleton reorganization in breast cancer cells. Oncotarget 7(43):70924–70935. doi:10.18632/oncotarget.12341
  147. 147.
    Luo LJ, Yang F, Ding JJ, Yan DL, Wang DD, Yang SJ, Ding L, Li J, Chen D, Ma R, Wu JZ, Tang JH (2016) MiR-31 inhibits migration and invasion by targeting SATB2 in triple negative breast cancer. Gene 594(1):47–58. doi: 10.1016/j.gene.2016.08.057 PubMedCrossRefGoogle Scholar
  148. 148.
    Billam M, Sobolewski MD, Davidson NE (2010) Effects of a novel DNA methyltransferase inhibitor zebularine on human breast cancer cells. Breast Cancer Res Treat 120(3):581–592. doi: 10.1007/s10549-009-0420-3 PubMedCrossRefGoogle Scholar
  149. 149.
    Chen M, Shabashvili D, Nawab A, Yang SX, Dyer LM, Brown KD, Hollingshead M, Hunter KW, Kaye FJ, Hochwald SN, Marquez VE, Steeg P, Zajac-Kaye M (2012) DNA methyltransferase inhibitor, zebularine, delays tumor growth and induces apoptosis in a genetically engineered mouse model of breast cancer. Mol Cancer Ther 11(2):370–382. doi: 10.1158/1535-7163.MCT-11-0458 PubMedCrossRefGoogle Scholar
  150. 150.
    Ceccacci E, Minucci S (2016) Inhibition of histone deacetylases in cancer therapy: lessons from leukaemia. Br J Cancer 114(6):605–611. doi: 10.1038/bjc.2016.36 PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    Miller L, Abdalla A (2003) The role of endoscopy in the treatment of esophageal varices, 2002-2003. Curr Opin Gastroenterol 19(5):483–486PubMedCrossRefGoogle Scholar
  152. 152.
    Yoshida M, Shimazu T, Matsuyama A (2003) Protein deacetylases: enzymes with functional diversity as novel therapeutic targets. Prog Cell Cycle Res 5:269–278PubMedGoogle Scholar
  153. 153.
    Marks PA, Breslow R (2007) Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug. Nat Biotechnol 25(1):84–90. doi: 10.1038/nbt1272 PubMedCrossRefGoogle Scholar
  154. 154.
    Chiaradonna F, Barozzi I, Miccolo C, Bucci G, Palorini R, Fornasari L, Botrugno OA, Pruneri G, Masullo M, Passafaro A, Galimberti VE, Fantin VR, Richon VM, Pece S, Viale G, Di Fiore PP, Draetta G, Pelicci PG, Minucci S, Chiocca S (2015) Redox-mediated Suberoylanilide Hydroxamic acid sensitivity in breast cancer. Antioxid Redox Signal 23(1):15–29. doi: 10.1089/ars.2014.6189 PubMedPubMedCentralCrossRefGoogle Scholar
  155. 155.
    Wu S, Luo Z, Yu PJ, Xie H, He YW (2016) Suberoylanilide hydroxamic acid (SAHA) promotes the epithelial mesenchymal transition of triple negative breast cancer cells via HDAC8/FOXA1 signals. Biol Chem 397(1):75–83. doi: 10.1515/hsz-2015-0215 PubMedCrossRefGoogle Scholar
  156. 156.
    Feng X, Han H, Zou D, Zhou J, Zhou W (2017) Suberoylanilide hydroxamic acid-induced specific epigenetic regulation controls leptin-induced proliferation of breast cancer cell lines. Oncotarget 8(2):3364–3379. doi:10.18632/oncotarget.13764
  157. 157.
    Han RF, Li K, Yang ZS, Chen ZG, Yang WC (2014) Trichostatin a induces mesenchymal-like morphological change and gene expression but inhibits migration and colony formation in human cancer cells. Mol Med Rep 10(6):3211–3216. doi: 10.3892/mmr.2014.2594 PubMedCrossRefGoogle Scholar
  158. 158.
    Chang J, Varghese DS, Gillam MC, Peyton M, Modi B, Schiltz RL, Girard L, Martinez ED (2012) Differential response of cancer cells to HDAC inhibitors trichostatin a and depsipeptide. Br J Cancer 106(1):116–125. doi: 10.1038/bjc.2011.532 PubMedCrossRefGoogle Scholar
  159. 159.
    Liu J, Li Y (2015) Trichostatin a and tamoxifen inhibit breast cancer cell growth by miR-204 and ERalpha reducing AKT/mTOR pathway. Biochem Biophys Res Commun 467(2):242–247. doi: 10.1016/j.bbrc.2015.09.182 PubMedCrossRefGoogle Scholar
  160. 160.
    Sun S, Han Y, Liu J, Fang Y, Tian Y, Zhou J, Ma D, Wu P (2014) Trichostatin a targets the mitochondrial respiratory chain, increasing mitochondrial reactive oxygen species production to trigger apoptosis in human breast cancer cells. PLoS One 9(3):e91610. doi: 10.1371/journal.pone.0091610 PubMedPubMedCentralCrossRefGoogle Scholar
  161. 161.
    Noh H, Park J, Shim M, Lee Y (2016) Trichostatin a enhances estrogen receptor-alpha repression in MCF-7 breast cancer cells under hypoxia. Biochem Biophys Res Commun 470(3):748–752. doi: 10.1016/j.bbrc.2016.01.022 PubMedCrossRefGoogle Scholar
  162. 162.
    Zhuang ZG, Fei F, Chen Y, Jin W (2008) Suberoyl bis-hydroxamic acid induces p53-dependent apoptosis of MCF-7 breast cancer cells. Acta Pharmacol Sin 29(12):1459–1466. doi: 10.1111/j.1745-7254.2008.00906.x PubMedCrossRefGoogle Scholar
  163. 163.
    Yang X, Zhang N, Shi Z, Yang Z, Hu X (2015) Histone deacetylase inhibitor suberoyl bis-hydroxamic acid suppresses cell proliferation and induces apoptosis in breast cancer cells. Mol Med Rep 11(4):2908–2912. doi: 10.3892/mmr.2014.3076 PubMedCrossRefGoogle Scholar
  164. 164.
    Fortunati N, Marano F, Bandino A, Frairia R, Catalano MG, Boccuzzi G (2014) The pan-histone deacetylase inhibitor LBH589 (panobinostat) alters the invasive breast cancer cell phenotype. Int J Oncol 44(3):700–708. doi: 10.3892/ijo.2013.2218 PubMedCrossRefGoogle Scholar
  165. 165.
    Tate CR, Rhodes LV, Segar HC, Driver JL, Pounder FN, Burow ME, Collins-Burow BM (2012) Targeting triple-negative breast cancer cells with the histone deacetylase inhibitor panobinostat. Breast Cancer Res 14(3):R79. doi: 10.1186/bcr3192 PubMedPubMedCentralCrossRefGoogle Scholar
  166. 166.
    Kubo M, Kanaya N, Petrossian K, Ye J, Warden C, Liu Z, Nishimura R, Osako T, Okido M, Shimada K, Takahashi M, Chu P, Yuan YC, Chen S (2013) Inhibition of the proliferation of acquired aromatase inhibitor-resistant breast cancer cells by histone deacetylase inhibitor LBH589 (panobinostat). Breast Cancer Res Treat 137(1):93–107. doi: 10.1007/s10549-012-2332-x PubMedCrossRefGoogle Scholar
  167. 167.
    Rhodes LV, Tate CR, Segar HC, Burks HE, Phamduy TB, Hoang V, Elliott S, Gilliam D, Pounder FN, Anbalagan M, Chrisey DB, Rowan BG, Burow ME, Collins-Burow BM (2014) Suppression of triple-negative breast cancer metastasis by pan-DAC inhibitor panobinostat via inhibition of ZEB family of EMT master regulators. Breast Cancer Res Treat 145(3):593–604. doi: 10.1007/s10549-014-2979-6 PubMedPubMedCentralCrossRefGoogle Scholar
  168. 168.
    Schech A, Kazi A, Yu S, Shah P, Sabnis G (2015) Histone deacetylase inhibitor Entinostat inhibits tumor-initiating cells in triple-negative breast cancer cells. Mol Cancer Ther 14(8):1848–1857. doi: 10.1158/1535-7163.MCT-14-0778 PubMedCrossRefGoogle Scholar
  169. 169.
    Schech AJ, Shah P, Yu S, Sabnis GJ, Goloubeva O, Rosenblatt P, Kazi A, Chumsri S, Brodie A (2015) Histone deacetylase inhibitor entinostat in combination with a retinoid downregulates HER2 and reduces the tumor initiating cell population in aromatase inhibitor-resistant breast cancer. Breast Cancer Res Treat 152(3):499–508. doi: 10.1007/s10549-015-3442-z PubMedCrossRefGoogle Scholar
  170. 170.
    Fortunati N, Bertino S, Costantino L, Bosco O, Vercellinatto I, Catalano MG, Boccuzzi G (2008) Valproic acid is a selective antiproliferative agent in estrogen-sensitive breast cancer cells. Cancer Lett 259(2):156–164. doi: 10.1016/j.canlet.2007.10.006 PubMedCrossRefGoogle Scholar
  171. 171.
    Artacho-Cordon F, Rios-Arrabal S, Olivares-Urbano MA, Storch K, Dickreuter E, Munoz-Gamez JA, Leon J, Calvente I, Torne P, Salinas Mdel M, Cordes N, Nunez MI (2015) Valproic acid modulates radiation-enhanced matrix metalloproteinase activity and invasion of breast cancer cells. Int J Radiat Biol 91(12):946–956. doi: 10.3109/09553002.2015.1087067 PubMedCrossRefGoogle Scholar
  172. 172.
    Vafaiyan Z, Gharaei R, Asadi J (2015) The correlation between telomerase activity and Bax/Bcl-2 ratio in valproic acid-treated MCF-7 breast cancer cell line. Iran J Basic Med Sci 18(7):700–704PubMedPubMedCentralGoogle Scholar
  173. 173.
    Mawatari T, Ninomiya I, Inokuchi M, Harada S, Hayashi H, Oyama K, Makino I, Nakagawara H, Miyashita T, Tajima H, Takamura H, Fushida S, Ohta T (2015) Valproic acid inhibits proliferation of HER2-expressing breast cancer cells by inducing cell cycle arrest and apoptosis through Hsp70 acetylation. Int J Oncol 47(6):2073–2081. doi: 10.3892/ijo.2015.3213 PubMedPubMedCentralCrossRefGoogle Scholar
  174. 174.
    Travaglini L, Vian L, Billi M, Grignani F, Nervi C (2009) Epigenetic reprogramming of breast cancer cells by valproic acid occurs regardless of estrogen receptor status. Int J Biochem Cell Biol 41(1):225–234. doi: 10.1016/j.biocel.2008.08.019 PubMedCrossRefGoogle Scholar
  175. 175.
    Chopin V, Toillon RA, Jouy N, Le Bourhis X (2002) Sodium butyrate induces P53-independent, Fas-mediated apoptosis in MCF-7 human breast cancer cells. Br J Pharmacol 135(1):79–86. doi: 10.1038/sj.bjp.0704456 PubMedPubMedCentralCrossRefGoogle Scholar
  176. 176.
    Louis M, Rosato RR, Brault L, Osbild S, Battaglia E, Yang XH, Grant S, Bagrel D (2004) The histone deacetylase inhibitor sodium butyrate induces breast cancer cell apoptosis through diverse cytotoxic actions including glutathione depletion and oxidative stress. Int J Oncol 25(6):1701–1711PubMedGoogle Scholar
  177. 177.
    Lee KW, Kim JH, Park JH, Kim HP, Song SH, Kim SG, Kim TY, Jong HS, Jung KH, Im SA, Kim TY, Kim NK, Bang YJ (2006) Antitumor activity of SK-7041, a novel histone deacetylase inhibitor, in human lung and breast cancer cells. Anticancer Res 26(5A):3429–3438PubMedGoogle Scholar
  178. 178.
    Hait NC, Avni D, Yamada A, Nagahashi M, Aoyagi T, Aoki H, Dumur CI, Zelenko Z, Gallagher EJ, Leroith D, Milstien S, Takabe K, Spiegel S (2015) The phosphorylated prodrug FTY720 is a histone deacetylase inhibitor that reactivates ERalpha expression and enhances hormonal therapy for breast cancer. Oncogene 4:e156. doi: 10.1038/oncsis.2015.16 CrossRefGoogle Scholar
  179. 179.
    Prestegui-Martel B, Bermudez-Lugo JA, Chavez-Blanco A, Duenas-Gonzalez A, Garcia-Sanchez JR, Perez-Gonzalez OA, Padilla M, II, Fragoso-Vazquez MJ, Mendieta-Wejebe JE, Correa-Basurto AM, Mendez-Luna D, Trujillo-Ferrara J, Correa-Basurto J (2016) N-(2-hydroxyphenyl)-2-propylpentanamide, a valproic acid aryl derivative designed in silico with improved anti-proliferative activity in HeLa, rhabdomyosarcoma and breast cancer cells. J Enzyme Inhib Med Chem 31(Suppl 3):140–149. doi: 10.1080/14756366.2016.1210138
  180. 180.
    Keen JC, Yan L, Mack KM, Pettit C, Smith D, Sharma D, Davidson NE (2003) A novel histone deacetylase inhibitor, scriptaid, enhances expression of functional estrogen receptor alpha (ER) in ER negative human breast cancer cells in combination with 5-aza 2′-deoxycytidine. Breast Cancer Res Treat 81(3):177–186. doi: 10.1023/A:1026146524737 PubMedCrossRefGoogle Scholar
  181. 181.
    Giacinti L, Giacinti C, Gabellini C, Rizzuto E, Lopez M, Giordano A (2012) Scriptaid effects on breast cancer cell lines. J Cell Physiol 227(10):3426–3433. doi: 10.1002/jcp.24043 PubMedCrossRefGoogle Scholar
  182. 182.
    Chiu HW, Yeh YL, Wang YC, Huang WJ, Ho SY, Lin P, Wang YJ (2016) Combination of the novel histone deacetylase inhibitor YCW1 and radiation induces autophagic cell death through the downregulation of BNIP3 in triple-negative breast cancer cells in vitro and in an orthotopic mouse model. Mol Cancer 15(1):46. doi: 10.1186/s12943-016-0531-5 PubMedPubMedCentralCrossRefGoogle Scholar
  183. 183.
    Gromek SM, deMayo JA, Maxwell AT, West AM, Pavlik CM, Zhao Z, Li J, Wiemer AJ, Zweifach A, Balunas MJ (2016) Synthesis and biological evaluation of santacruzamate a analogues for anti-proliferative and immunomodulatory activity. Bioorg Med Chem 24(21):5183–5196. doi: 10.1016/j.bmc.2016.08.040 PubMedPubMedCentralCrossRefGoogle Scholar
  184. 184.
    Tan YL, Pigeon P, Top S, Labbe E, Buriez O, Hillard EA, Vessieres A, Amatore C, Leong WK, Jaouen G (2012) Ferrocenyl catechols: synthesis, oxidation chemistry and anti-proliferative effects on MDA-MB-231 breast cancer cells. Dalton Trans 41(25):7537–7549. doi: 10.1039/c2dt30700f PubMedCrossRefGoogle Scholar
  185. 185.
    Zheng Y, Wang C, Li C, Qiao J, Zhang F, Huang M, Ren W, Dong C, Huang J, Zhou HB (2012) Discovery of novel SERMs with a ferrocenyl entity based on the oxabicyclo[2.2.1]heptene scaffold and evaluation of their antiproliferative effects in breast cancer cells. Org Biomol Chem 10(48):9689–9699. doi: 10.1039/c2ob26226f PubMedCrossRefGoogle Scholar
  186. 186.
    Laine AL, Adriaenssens E, Vessieres A, Jaouen G, Corbet C, Desruelles E, Pigeon P, Toillon RA, Passirani C (2013) The in vivo performance of ferrocenyl tamoxifen lipid nanocapsules in xenografted triple negative breast cancer. Biomaterials 34(28):6949–6956. doi: 10.1016/j.biomaterials.2013.05.065 PubMedCrossRefGoogle Scholar
  187. 187.
    Li C, Tang C, Hu Z, Zhao C, Li C, Zhang S, Dong C, Zhou HB, Huang J (2016) Synthesis and structure-activity relationships of novel hybrid ferrocenyl compounds based on a bicyclic core skeleton for breast cancer therapy. Bioorg Med Chem 24(13):3062–3074. doi: 10.1016/j.bmc.2016.05.019 PubMedCrossRefGoogle Scholar
  188. 188.
    Thakur S, Feng X, Qiao Shi Z, Ganapathy A, Kumar Mishra M, Atadja P, Morris D, Riabowol K (2012) ING1 and 5-azacytidine act synergistically to block breast cancer cell growth. PLoS One 7(8):e43671. doi: 10.1371/journal.pone.0043671 PubMedPubMedCentralCrossRefGoogle Scholar
  189. 189.
    Zhou W, Feng X, Han H, Guo S, Wang G (2016) Synergistic effects of combined treatment with histone deacetylase inhibitor suberoylanilide hydroxamic acid and TRAIL on human breast cancer cells. Sci Rep 6:28004. doi: 10.1038/srep28004 PubMedPubMedCentralCrossRefGoogle Scholar
  190. 190.
    Min A, Im SA, Kim DK, Song SH, Kim HJ, Lee KH, Kim TY, Han SW, Oh DY, Kim TY, O'Connor MJ, Bang YJ (2015) Histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), enhances anti-tumor effects of the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib in triple-negative breast cancer cells. Breast Cancer Res 17:33. doi: 10.1186/s13058-015-0534-y PubMedPubMedCentralCrossRefGoogle Scholar
  191. 191.
    Chen L, Jin T, Zhu K, Piao Y, Quan T, Quan C, Lin Z (2017) PI3K/mTOR dual inhibitor BEZ235 and histone deacetylase inhibitor Trichostatin A synergistically exert anti-tumor activity in breast cancer. Oncotarget. doi:10.18632/oncotarget.14442
  192. 192.
    Yang X, Shi Z, Zhang N, Ou Z, Fu S, Hu X, Shen Z (2014) Suberoyl bis-hydroxamic acid enhances cytotoxicity induced by proteasome inhibitors in breast cancer cells. Cancer Cell Int 14:107. doi: 10.1186/s12935-014-0107-7 PubMedPubMedCentralCrossRefGoogle Scholar
  193. 193.
    Lin Z, Zhang Z, Jiang X, Kou X, Bao Y, Liu H, Sun F, Ling S, Qin N, Jiang L, Yang Y (2017) Mevastatin blockade of autolysosome maturation stimulates LBH589-induced cell death in triple-negative breast cancer cells. Oncotarget. doi:10.18632/oncotarget.14868
  194. 194.
    Kai M, Kanaya N, Wu SV, Mendez C, Nguyen D, Luu T, Chen S (2015) Targeting breast cancer stem cells in triple-negative breast cancer using a combination of LBH589 and salinomycin. Breast Cancer Res Treat 151(2):281–294. doi: 10.1007/s10549-015-3376-5 PubMedPubMedCentralCrossRefGoogle Scholar
  195. 195.
    Tan WW, Allred JB, Moreno-Aspitia A, Northfelt DW, Ingle JN, Goetz MP, Perez EA (2016) Phase I study of Panobinostat (LBH589) and Letrozole in postmenopausal metastatic breast cancer patients. Clin Breast Cancer 16(2):82–86. doi: 10.1016/j.clbc.2015.11.003 PubMedCrossRefGoogle Scholar
  196. 196.
    Ou O, Huppi K, Chakka S, Gehlhaus K, Dubois W, Patel J, Chen J, Mackiewicz M, Jones TL, Pitt JJ, Martin SE, Goldsmith P, Simmons JK, Mock BA, Caplen NJ (2014) Loss-of-function RNAi screens in breast cancer cells identify AURKB, PLK1, PIK3R1, MAPK12, PRKD2, and PTK6 as sensitizing targets of rapamycin activity. Cancer Lett 354(2):336–347. doi: 10.1016/j.canlet.2014.08.043 PubMedPubMedCentralCrossRefGoogle Scholar
  197. 197.
    Terranova-Barberio M, Roca MS, Zotti AI, Leone A, Bruzzese F, Vitagliano C, Scogliamiglio G, Russo D, D'Angelo G, Franco R, Budillon A, Di Gennaro E (2016) Valproic acid potentiates the anticancer activity of capecitabine in vitro and in vivo in breast cancer models via induction of thymidine phosphorylase expression. Oncotarget 7(7):7715–7731. doi:10.18632/oncotarget.6802
  198. 198.
    Li L, Sun Y, Liu J, Wu X, Chen L, Ma L, Wu P (2015) Histone deacetylase inhibitor sodium butyrate suppresses DNA double strand break repair induced by etoposide more effectively in MCF-7 cells than in HEK293 cells. BMC Biochem 16:2. doi: 10.1186/s12858-014-0030-5 PubMedPubMedCentralCrossRefGoogle Scholar
  199. 199.
    Sun B, Liu R, Xiao ZD, Zhu X (2012) C-MET protects breast cancer cells from apoptosis induced by sodium butyrate. PLoS one 7 (1):e30143. doi: 10.1371/journal.pone.0030143
  200. 200.
    Cava C, Bertoli G, Castiglioni I (2015) Integrating genetics and epigenetics in breast cancer: biological insights, experimental, computational methods and therapeutic potential. BMC Syst Biol 9:62. doi: 10.1186/s12918-015-0211-x PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  • Sumin Oh
    • 1
  • Je Yeong Ko
    • 1
  • Chaeun Oh
    • 1
  • Kyung Hyun Yoo
    • 1
    Email author
  1. 1.Department of Biological SciencesSookmyung Women’s UniversitySeoulSouth Korea

Personalised recommendations