Multifaceted role of EZH2 in breast and prostate tumorigenesis

References

• Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144:646 - 74; http://dx.doi.org/10.1016/j.cell.2011.02.013; PMID: 21376230
   PubMed Web of Science ®Google Scholar
• You JS, Jones PA. Cancer genetics and epigenetics: two sides of the same coin?. Cancer Cell 2012; 22:9 - 20; http://dx.doi.org/10.1016/j.ccr.2012.06.008; PMID: 22789535
   PubMed Web of Science ®Google Scholar
• Rodríguez-Paredes M, Esteller M. Cancer epigenetics reaches mainstream oncology. Nat Med 2011; 17:330 - 9; http://dx.doi.org/10.1038/nm.2305; PMID: 21386836
   PubMed Web of Science ®Google Scholar
• Wilson BG, Roberts CW. SWI/SNF nucleosome remodellers and cancer. Nat Rev Cancer 2011; 11:481 - 92; http://dx.doi.org/10.1038/nrc3068; PMID: 21654818
   PubMed Web of Science ®Google Scholar
• Jenuwein T, Laible G, Dorn R, Reuter G. SET domain proteins modulate chromatin domains in eu- and heterochromatin. Cell Mol Life Sci 1998; 54:80 - 93; http://dx.doi.org/10.1007/s000180050127; PMID: 9487389
   PubMed Web of Science ®Google Scholar
• Tachibana M, Ueda J, Fukuda M, Takeda N, Ohta T, Iwanari H, et al. Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9. Genes Dev 2005; 19:815 - 26; http://dx.doi.org/10.1101/gad.1284005; PMID: 15774718
   PubMed Web of Science ®Google Scholar
• Stewart MD, Li J, Wong J. Relationship between histone H3 lysine 9 methylation, transcription repression, and heterochromatin protein 1 recruitment. Mol Cell Biol 2005; 25:2525 - 38; http://dx.doi.org/10.1128/MCB.25.7.2525-2538.2005; PMID: 15767660
   PubMed Web of Science ®Google Scholar
• Jenuwein T, Allis CD. Translating the histone code. Science 2001; 293:1074 - 80; http://dx.doi.org/10.1126/science.1063127; PMID: 11498575
   PubMed Web of Science ®Google Scholar
• Cao R, Zhang Y. The functions of E(Z)/EZH2-mediated methylation of lysine 27 in histone H3. Curr Opin Genet Dev 2004; 14:155 - 64; http://dx.doi.org/10.1016/j.gde.2004.02.001; PMID: 15196462
   PubMed Web of Science ®Google Scholar
• Schuettengruber B, Chourrout D, Vervoort M, Leblanc B, Cavalli G. Genome regulation by polycomb and trithorax proteins. Cell 2007; 128:735 - 45; http://dx.doi.org/10.1016/j.cell.2007.02.009; PMID: 17320510
   PubMed Web of Science ®Google Scholar
• Boyer LA, Plath K, Zeitlinger J, Brambrink T, Medeiros LA, Lee TI, et al. Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 2006; 441:349 - 53; http://dx.doi.org/10.1038/nature04733; PMID: 16625203
   PubMed Web of Science ®Google Scholar
• Sauvageau M, Sauvageau G. Polycomb group proteins: multi-faceted regulators of somatic stem cells and cancer. Cell Stem Cell 2010; 7:299 - 313; http://dx.doi.org/10.1016/j.stem.2010.08.002; PMID: 20804967
   PubMed Web of Science ®Google Scholar
• Kondo Y, Shen L, Cheng AS, Ahmed S, Boumber Y, Charo C, et al. Gene silencing in cancer by histone H3 lysine 27 trimethylation independent of promoter DNA methylation. Nat Genet 2008; 40:741 - 50; http://dx.doi.org/10.1038/ng.159; PMID: 18488029
   PubMed Web of Science ®Google Scholar
• Rush M, Appanah R, Lee S, Lam LL, Goyal P, Lorincz MC. Targeting of EZH2 to a defined genomic site is sufficient for recruitment of Dnmt3a but not de novo DNA methylation. Epigenetics 2009; 4:404 - 14; http://dx.doi.org/10.4161/epi.4.6.9392; PMID: 19717977
   PubMed Web of Science ®Google Scholar
• Kleer CG, Cao Q, Varambally S, Shen R, Ota I, Tomlins SA, et al. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc Natl Acad Sci U S A 2003; 100:11606 - 11; http://dx.doi.org/10.1073/pnas.1933744100; PMID: 14500907
   PubMed Web of Science ®Google Scholar
• Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar-Sinha C, Sanda MG, et al. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature 2002; 419:624 - 9; http://dx.doi.org/10.1038/nature01075; PMID: 12374981
   PubMed Web of Science ®Google Scholar
• Rau KM, Kang HY, Cha TL, Miller SA, Hung MC. The mechanisms and managements of hormone-therapy resistance in breast and prostate cancers. Endocr Relat Cancer 2005; 12:511 - 32; http://dx.doi.org/10.1677/erc.1.01026; PMID: 16172190
   PubMed Web of Science ®Google Scholar
• Xu K, Wu ZJ, Groner AC, He HH, Cai C, Lis RT, et al. EZH2 oncogenic activity in castration-resistant prostate cancer cells is Polycomb-independent. Science 2012; 338:1465 - 9; http://dx.doi.org/10.1126/science.1227604; PMID: 23239736
   PubMed Web of Science ®Google Scholar
• Cavalli G. Molecular biology. EZH2 goes solo. Science 2012; 338:1430 - 1; http://dx.doi.org/10.1126/science.1232332; PMID: 23239724
   PubMed Web of Science ®Google Scholar
• Lee ST, Li Z, Wu Z, Aau M, Guan P, Karuturi RK, et al. Context-specific regulation of NF-κB target gene expression by EZH2 in breast cancers. Mol Cell 2011; 43:798 - 810; http://dx.doi.org/10.1016/j.molcel.2011.08.011; PMID: 21884980
   PubMed Web of Science ®Google Scholar
• Shi B, Liang J, Yang X, Wang Y, Zhao Y, Wu H, et al. Integration of estrogen and Wnt signaling circuits by the polycomb group protein EZH2 in breast cancer cells. Mol Cell Biol 2007; 27:5105 - 19; http://dx.doi.org/10.1128/MCB.00162-07; PMID: 17502350
   PubMed Web of Science ®Google Scholar
• Lewis EB. A gene complex controlling segmentation in Drosophila. Nature 1978; 276:565 - 70; http://dx.doi.org/10.1038/276565a0; PMID: 103000
   PubMed Web of Science ®Google Scholar
• Yu M, Mazor T, Huang H, Huang HT, Kathrein KL, Woo AJ, et al. Direct recruitment of polycomb repressive complex 1 to chromatin by core binding transcription factors. Mol Cell 2012; 45:330 - 43; http://dx.doi.org/10.1016/j.molcel.2011.11.032; PMID: 22325351
   PubMed Web of Science ®Google Scholar
• Levine SS, Weiss A, Erdjument-Bromage H, Shao Z, Tempst P, Kingston RE. The core of the polycomb repressive complex is compositionally and functionally conserved in flies and humans. Mol Cell Biol 2002; 22:6070 - 8; http://dx.doi.org/10.1128/MCB.22.17.6070-6078.2002; PMID: 12167701
   PubMed Web of Science ®Google Scholar
• Wang L, Brown JL, Cao R, Zhang Y, Kassis JA, Jones RS. Hierarchical recruitment of polycomb group silencing complexes. Mol Cell 2004; 14:637 - 46; http://dx.doi.org/10.1016/j.molcel.2004.05.009; PMID: 15175158
   PubMed Web of Science ®Google Scholar
• Yap KL, Li S, Muñoz-Cabello AM, Raguz S, Zeng L, Mujtaba S, et al. Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Mol Cell 2010; 38:662 - 74; http://dx.doi.org/10.1016/j.molcel.2010.03.021; PMID: 20541999
   PubMed Web of Science ®Google Scholar
• Shao Z, Raible F, Mollaaghababa R, Guyon JR, Wu CT, Bender W, et al. Stabilization of chromatin structure by PRC1, a Polycomb complex. Cell 1999; 98:37 - 46; http://dx.doi.org/10.1016/S0092-8674(00)80604-2; PMID: 10412979
   PubMed Web of Science ®Google Scholar
• Margueron R, Li G, Sarma K, Blais A, Zavadil J, Woodcock CL, et al. Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms. Mol Cell 2008; 32:503 - 18; http://dx.doi.org/10.1016/j.molcel.2008.11.004; PMID: 19026781
   PubMed Web of Science ®Google Scholar
• Kim H, Kang K, Kim J. AEBP2 as a potential targeting protein for Polycomb Repression Complex PRC2. Nucleic Acids Res 2009; 37:2940 - 50; http://dx.doi.org/10.1093/nar/gkp149; PMID: 19293275
   PubMed Web of Science ®Google Scholar
• Nekrasov M, Klymenko T, Fraterman S, Papp B, Oktaba K, Köcher T, et al. Pcl-PRC2 is needed to generate high levels of H3-K27 trimethylation at Polycomb target genes. EMBO J 2007; 26:4078 - 88; http://dx.doi.org/10.1038/sj.emboj.7601837; PMID: 17762866
   PubMed Web of Science ®Google Scholar
• Walker E, Chang WY, Hunkapiller J, Cagney G, Garcha K, Torchia J, et al. Polycomb-like 2 associates with PRC2 and regulates transcriptional networks during mouse embryonic stem cell self-renewal and differentiation. Cell Stem Cell 2010; 6:153 - 66; http://dx.doi.org/10.1016/j.stem.2009.12.014; PMID: 20144788
   PubMed Web of Science ®Google Scholar
• Abel KJ, Brody LC, Valdes JM, Erdos MR, McKinley DR, Castilla LH, et al. Characterization of EZH1, a human homolog of Drosophila Enhancer of zeste near BRCA1. Genomics 1996; 37:161 - 71; http://dx.doi.org/10.1006/geno.1996.0537; PMID: 8921387
   PubMed Web of Science ®Google Scholar
• Bracken AP, Pasini D, Capra M, Prosperini E, Colli E, Helin K. EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer. EMBO J 2003; 22:5323 - 35; http://dx.doi.org/10.1093/emboj/cdg542; PMID: 14532106
   PubMed Web of Science ®Google Scholar
• Cardoso C, Mignon C, Hetet G, Grandchamps B, Fontes M, Colleaux L. The human EZH2 gene: genomic organisation and revised mapping in 7q35 within the critical region for malignant myeloid disorders. Eur J Hum Genet 2000; 8:174 - 80; http://dx.doi.org/10.1038/sj.ejhg.5200439; PMID: 10780782
   PubMed Web of Science ®Google Scholar
• Margueron R, Reinberg D. The Polycomb complex PRC2 and its mark in life. Nature 2011; 469:343 - 9; http://dx.doi.org/10.1038/nature09784; PMID: 21248841
   PubMed Web of Science ®Google Scholar
• Chase A, Cross NC. Aberrations of EZH2 in cancer. Clin Cancer Res 2011; 17:2613 - 8; http://dx.doi.org/10.1158/1078-0432.CCR-10-2156; PMID: 21367748
   PubMed Web of Science ®Google Scholar
• Morin RD, Johnson NA, Severson TM, Mungall AJ, An J, Goya R, et al. Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. Nat Genet 2010; 42:181 - 5; http://dx.doi.org/10.1038/ng.518; PMID: 20081860
   PubMed Web of Science ®Google Scholar
• Ernst T, Chase AJ, Score J, Hidalgo-Curtis CE, Bryant C, Jones AV, et al. Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders. Nat Genet 2010; 42:722 - 6; http://dx.doi.org/10.1038/ng.621; PMID: 20601953
   PubMed Web of Science ®Google Scholar
• Nikoloski G, Langemeijer SMC, Kuiper RP, Knops R, Massop M, Tönnissen ERLTM, et al. Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes. Nat Genet 2010; 42:665 - 7; http://dx.doi.org/10.1038/ng.620; PMID: 20601954
   PubMed Web of Science ®Google Scholar
• Cha TL, Zhou BP, Xia W, Wu Y, Yang CC, Chen CT, et al. Akt-mediated phosphorylation of EZH2 suppresses methylation of lysine 27 in histone H3. Science 2005; 310:306 - 10; http://dx.doi.org/10.1126/science.1118947; PMID: 16224021
   PubMed Web of Science ®Google Scholar
• Chen S, Bohrer LR, Rai AN, Pan Y, Gan L, Zhou X, et al. Cyclin-dependent kinases regulate epigenetic gene silencing through phosphorylation of EZH2. Nat Cell Biol 2010; 12:1108 - 14; http://dx.doi.org/10.1038/ncb2116; PMID: 20935635
   PubMed Web of Science ®Google Scholar
• Riising EM, Boggio R, Chiocca S, Helin K, Pasini D. The polycomb repressive complex 2 is a potential target of SUMO modifications. PLoS One 2008; 3:e2704; http://dx.doi.org/10.1371/journal.pone.0002704; PMID: 18628979
   PubMedGoogle Scholar
• Ku M, Koche RP, Rheinbay E, Mendenhall EM, Endoh M, Mikkelsen TS, et al. Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains. PLoS Genet 2008; 4:e1000242; http://dx.doi.org/10.1371/journal.pgen.1000242; PMID: 18974828
   PubMed Web of Science ®Google Scholar
• Wilkinson FH, Park K, Atchison ML. Polycomb recruitment to DNA in vivo by the YY1 REPO domain. Proc Natl Acad Sci U S A 2006; 103:19296 - 301; http://dx.doi.org/10.1073/pnas.0603564103; PMID: 17158804
   PubMed Web of Science ®Google Scholar
• Xi H, Yu Y, Fu Y, Foley J, Halees A, Weng Z. Analysis of overrepresented motifs in human core promoters reveals dual regulatory roles of YY1. Genome Res 2007; 17:798 - 806; http://dx.doi.org/10.1101/gr.5754707; PMID: 17567998
   PubMed Web of Science ®Google Scholar
• Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 2007; 129:1311 - 23; http://dx.doi.org/10.1016/j.cell.2007.05.022; PMID: 17604720
   PubMed Web of Science ®Google Scholar
• Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, et al. Long noncoding RNA as modular scaffold of histone modification complexes. Science 2010; 329:689 - 93; http://dx.doi.org/10.1126/science.1192002; PMID: 20616235
   PubMed Web of Science ®Google Scholar
• Plath K, Fang J, Mlynarczyk-Evans SK, Cao R, Worringer KA, Wang H, et al. Role of histone H3 lysine 27 methylation in X inactivation. Science 2003; 300:131 - 5; http://dx.doi.org/10.1126/science.1084274; PMID: 12649488
   PubMed Web of Science ®Google Scholar
• Maenner S, Blaud M, Fouillen L, Savoye A, Marchand V, Dubois A, et al. 2-D structure of the A region of Xist RNA and its implication for PRC2 association. PLoS Biol 2010; 8:e1000276; http://dx.doi.org/10.1371/journal.pbio.1000276; PMID: 20052282
   PubMed Web of Science ®Google Scholar
• Kohlmaier A, Savarese F, Lachner M, Martens J, Jenuwein T, Wutz A. A chromosomal memory triggered by Xist regulates histone methylation in X inactivation. PLoS Biol 2004; 2:E171; http://dx.doi.org/10.1371/journal.pbio.0020171; PMID: 15252442
   PubMedGoogle Scholar
• Pandey RR, Mondal T, Mohammad F, Enroth S, Redrup L, Komorowski J, et al. Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. Mol Cell 2008; 32:232 - 46; http://dx.doi.org/10.1016/j.molcel.2008.08.022; PMID: 18951091
   PubMed Web of Science ®Google Scholar
• Eskeland R, Leeb M, Grimes GR, Kress C, Boyle S, Sproul D, et al. Ring1B compacts chromatin structure and represses gene expression independent of histone ubiquitination. Mol Cell 2010; 38:452 - 64; http://dx.doi.org/10.1016/j.molcel.2010.02.032; PMID: 20471950
   PubMed Web of Science ®Google Scholar
• Schoeftner S, Sengupta AK, Kubicek S, Mechtler K, Spahn L, Koseki H, et al. Recruitment of PRC1 function at the initiation of X inactivation independent of PRC2 and silencing. EMBO J 2006; 25:3110 - 22; http://dx.doi.org/10.1038/sj.emboj.7601187; PMID: 16763550
   PubMed Web of Science ®Google Scholar
• Ko S, Ahn J, Song CS, Kim S, Knapczyk-Stwora K, Chatterjee B. Lysine methylation and functional modulation of androgen receptor by Set9 methyltransferase. Mol Endocrinol 2011; 25:433 - 44; http://dx.doi.org/10.1210/me.2010-0482; PMID: 21273441
   PubMed Web of Science ®Google Scholar
• Gaughan L, Stockley J, Wang N, McCracken SRC, Treumann A, Armstrong K, et al. Regulation of the androgen receptor by SET9-mediated methylation. Nucleic Acids Res 2011; 39:1266 - 79; http://dx.doi.org/10.1093/nar/gkq861; PMID: 20959290
   PubMed Web of Science ®Google Scholar
• Nan X, Ng H-H, Johnson CA, Laherty CD, Turner BM, Eisenman RN, et al. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 1998; 393:386 - 9; http://dx.doi.org/10.1038/30764; PMID: 9620804
   PubMed Web of Science ®Google Scholar
• Jones PL, Veenstra GJ, Wade PA, Vermaak D, Kass SU, Landsberger N, et al. Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet 1998; 19:187 - 91; http://dx.doi.org/10.1038/561; PMID: 9620779
   PubMed Web of Science ®Google Scholar
• Simon JA, Lange CA. Roles of the EZH2 histone methyltransferase in cancer epigenetics. Mutat Res 2008; 647:21 - 9; http://dx.doi.org/10.1016/j.mrfmmm.2008.07.010; PMID: 18723033
   PubMed Web of Science ®Google Scholar
• Viré E, Brenner C, Deplus R, Blanchon L, Fraga M, Didelot C, et al. The Polycomb group protein EZH2 directly controls DNA methylation. Nature 2006; 439:871 - 4; http://dx.doi.org/10.1038/nature04431; PMID: 16357870
   PubMed Web of Science ®Google Scholar
• McGarvey KM, Greene E, Fahrner JA, Jenuwein T, Baylin SB. DNA methylation and complete transcriptional silencing of cancer genes persist after depletion of EZH2. Cancer Res 2007; 67:5097 - 102; http://dx.doi.org/10.1158/0008-5472.CAN-06-2029; PMID: 17545586
   PubMed Web of Science ®Google Scholar
• Ohm JE, McGarvey KM, Yu X, Cheng L, Schuebel KE, Cope L, et al. A stem cell-like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing. Nat Genet 2007; 39:237 - 42; http://dx.doi.org/10.1038/ng1972; PMID: 17211412
   PubMed Web of Science ®Google Scholar
• Schlesinger Y, Straussman R, Keshet I, Farkash S, Hecht M, Zimmerman J, et al. Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer. Nat Genet 2007; 39:232 - 6; http://dx.doi.org/10.1038/ng1950; PMID: 17200670
   PubMed Web of Science ®Google Scholar
• Widschwendter M, Fiegl H, Egle D, Mueller-Holzner E, Spizzo G, Marth C, et al. Epigenetic stem cell signature in cancer. Nat Genet 2007; 39:157 - 8; http://dx.doi.org/10.1038/ng1941; PMID: 17200673
   PubMed Web of Science ®Google Scholar
• Barski A, Cuddapah S, Cui K, Roh T-Y, Schones DE, Wang Z, et al. High-resolution profiling of histone methylations in the human genome. Cell 2007; 129:823 - 37; http://dx.doi.org/10.1016/j.cell.2007.05.009; PMID: 17512414
   PubMed Web of Science ®Google Scholar
• Bell O, Wirbelauer C, Hild M, Scharf AND, Schwaiger M, MacAlpine DM, et al. Localized H3K36 methylation states define histone H4K16 acetylation during transcriptional elongation in Drosophila. EMBO J 2007; 26:4974 - 84; http://dx.doi.org/10.1038/sj.emboj.7601926; PMID: 18007591
   PubMed Web of Science ®Google Scholar
• Barrand S, Andersen IS, Collas P. Promoter-exon relationship of H3 lysine 9, 27, 36 and 79 methylation on pluripotency-associated genes. Biochem Biophys Res Commun 2010; 401:611 - 7; http://dx.doi.org/10.1016/j.bbrc.2010.09.116; PMID: 20920475
   PubMed Web of Science ®Google Scholar
• Schmitges FW, Prusty AB, Faty M, Stützer A, Lingaraju GM, Aiwazian J, et al. Histone methylation by PRC2 is inhibited by active chromatin marks. Mol Cell 2011; 42:330 - 41; http://dx.doi.org/10.1016/j.molcel.2011.03.025; PMID: 21549310
   PubMed Web of Science ®Google Scholar
• Yuan W, Xu M, Huang C, Liu N, Chen S, Zhu B. H3K36 methylation antagonizes PRC2-mediated H3K27 methylation. J Biol Chem 2011; 286:7983 - 9; http://dx.doi.org/10.1074/jbc.M110.194027; PMID: 21239496
   PubMed Web of Science ®Google Scholar
• Tie F, Banerjee R, Stratton CA, Prasad-Sinha J, Stepanik V, Zlobin A, et al. CBP-mediated acetylation of histone H3 lysine 27 antagonizes Drosophila Polycomb silencing. Development 2009; 136:3131 - 41; http://dx.doi.org/10.1242/dev.037127; PMID: 19700617
   PubMed Web of Science ®Google Scholar
• Pasini D, Malatesta M, Jung HR, Walfridsson J, Willer A, Olsson L, et al. Characterization of an antagonistic switch between histone H3 lysine 27 methylation and acetylation in the transcriptional regulation of Polycomb group target genes. Nucleic Acids Res 2010; 38:4958 - 69; http://dx.doi.org/10.1093/nar/gkq244; PMID: 20385584
   PubMed Web of Science ®Google Scholar
• Schwartz YB, Kahn TG, Stenberg P, Ohno K, Bourgon R, Pirrotta V. Alternative epigenetic chromatin states of polycomb target genes. PLoS Genet 2010; 6:e1000805; http://dx.doi.org/10.1371/journal.pgen.1000805; PMID: 20062800
   PubMed Web of Science ®Google Scholar
• Lau PNI, Cheung P. Histone code pathway involving H3 S28 phosphorylation and K27 acetylation activates transcription and antagonizes polycomb silencing. Proc Natl Acad Sci U S A 2011; 108:2801 - 6; http://dx.doi.org/10.1073/pnas.1012798108; PMID: 21282660
   PubMed Web of Science ®Google Scholar
• Gehani SS, Agrawal-Singh S, Dietrich N, Christophersen NS, Helin K, Hansen K. Polycomb group protein displacement and gene activation through MSK-dependent H3K27me3S28 phosphorylation. Mol Cell 2010; 39:886 - 900; http://dx.doi.org/10.1016/j.molcel.2010.08.020; PMID: 20864036
   PubMed Web of Science ®Google Scholar
• O’Meara MM, Simon JA. Inner workings and regulatory inputs that control Polycomb repressive complex 2. Chromosoma 2012; 121:221 - 34; http://dx.doi.org/10.1007/s00412-012-0361-1; PMID: 22349693
   PubMed Web of Science ®Google Scholar
• DeSantis C, Siegel R, Bandi P, Jemal A. Breast cancer statistics, 2011. CA Cancer J Clin 2011; 61:409 - 18; http://dx.doi.org/10.3322/caac.20134; PMID: 21969133
   PubMed Web of Science ®Google Scholar
• Ross JS, Fletcher JA. The HER-2/neu Oncogene in Breast Cancer: Prognostic Factor, Predictive Factor, and Target for Therapy. Oncologist 1998; 3:237 - 52; PMID: 10388110
   PubMedGoogle Scholar
• Hayes DF, Trock B, Harris AL. Assessing the clinical impact of prognostic factors: when is “statistically significant” clinically useful?. Breast Cancer Res Treat 1998; 52:305 - 19; http://dx.doi.org/10.1023/A:1006197805041; PMID: 10066089
   PubMed Web of Science ®Google Scholar
• Hayes DF. Do we need prognostic factors in nodal-negative breast cancer? Arbiter. Eur J Cancer 2000; 36:302 - 6; http://dx.doi.org/10.1016/S0959-8049(99)00303-2; PMID: 10708930
   PubMed Web of Science ®Google Scholar
• Collett K, Eide GE, Arnes J, Stefansson IM, Eide J, Braaten A, 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. Clin Cancer Res 2006; 12:1168 - 74; http://dx.doi.org/10.1158/1078-0432.CCR-05-1533; PMID: 16489070
   PubMed Web of Science ®Google Scholar
• Bachmann IM, Halvorsen OJ, Collett K, Stefansson IM, Straume O, Haukaas SA, et al. EZH2 expression is associated with high proliferation rate and aggressive tumor subgroups in cutaneous melanoma and cancers of the endometrium, prostate, and breast. J Clin Oncol 2006; 24:268 - 73; http://dx.doi.org/10.1200/JCO.2005.01.5180; PMID: 16330673
   PubMed Web of Science ®Google Scholar
• Gonzalez ME, Li X, Toy K, DuPrie M, Ventura AC, Banerjee M, et al. Downregulation of EZH2 decreases growth of estrogen receptor-negative invasive breast carcinoma and requires BRCA1. Oncogene 2009; 28:843 - 53; http://dx.doi.org/10.1038/onc.2008.433; PMID: 19079346
   PubMed Web of Science ®Google Scholar
• Du J, Li L, Ou Z, Kong C, Zhang Y, Dong Z, et al. FOXC1, a target of polycomb, inhibits metastasis of breast cancer cells. Breast Cancer Res Treat 2012; 131:65 - 73; http://dx.doi.org/10.1007/s10549-011-1396-3; PMID: 21465172
   PubMed Web of Science ®Google Scholar
• Zeidler M, Varambally S, Cao Q, Chinnaiyan AM, Ferguson DO, Merajver SD, et al. The Polycomb group protein EZH2 impairs DNA repair in breast epithelial cells. Neoplasia 2005; 7:1011 - 9; http://dx.doi.org/10.1593/neo.05472; PMID: 16331887
   PubMed Web of Science ®Google Scholar
• Yang X, Karuturi RK, Sun F, Aau M, Yu K, Shao R, et al. CDKN1C (p57) is a direct target of EZH2 and suppressed by multiple epigenetic mechanisms in breast cancer cells. PLoS One 2009; 4:e5011; http://dx.doi.org/10.1371/journal.pone.0005011; PMID: 19340297
   PubMed Web of Science ®Google Scholar
• Fujii S, Ito K, Ito Y, Ochiai A. Enhancer of zeste homologue 2 (EZH2) down-regulates RUNX3 by increasing histone H3 methylation. J Biol Chem 2008; 283:17324 - 32; http://dx.doi.org/10.1074/jbc.M800224200; PMID: 18430739
   PubMed Web of Science ®Google Scholar
• Ren G, Baritaki S, Marathe H, Feng J, Park S, Beach S, et al. Polycomb protein EZH2 regulates tumor invasion via the transcriptional repression of the metastasis suppressor RKIP in breast and prostate cancer. Cancer Res 2012; 72:3091 - 104; http://dx.doi.org/10.1158/0008-5472.CAN-11-3546; PMID: 22505648
   PubMed Web of Science ®Google Scholar
• Truax AD, Thakkar M, Greer SF. Dysregulated recruitment of the histone methyltransferase EZH2 to the class II transactivator (CIITA) promoter IV in breast cancer cells. PLoS One 2012; 7:e36013; http://dx.doi.org/10.1371/journal.pone.0036013; PMID: 22563434
   PubMedGoogle Scholar
• Taniguchi H, Jacinto FV, Villanueva A, Fernandez AF, Yamamoto H, Carmona FJ, et al. Silencing of Kruppel-like factor 2 by the histone methyltransferase EZH2 in human cancer. Oncogene 2012; 31:1988 - 94; http://dx.doi.org/10.1038/onc.2011.387; PMID: 21892211
   PubMed Web of Science ®Google Scholar
• Gonzalez ME, DuPrie ML, Krueger H, Merajver SD, Ventura AC, Toy KA, et al. Histone methyltransferase EZH2 induces Akt-dependent genomic instability and BRCA1 inhibition in breast cancer. Cancer Res 2011; 71:2360 - 70; http://dx.doi.org/10.1158/0008-5472.CAN-10-1933; PMID: 21406404
   PubMed Web of Science ®Google Scholar
• Dyson N. The regulation of E2F by pRB-family proteins. Genes Dev 1998; 12:2245 - 62; http://dx.doi.org/10.1101/gad.12.15.2245; PMID: 9694791
   PubMed Web of Science ®Google Scholar
• Helin K. Regulation of cell proliferation by the E2F transcription factors. Curr Opin Genet Dev 1998; 8:28 - 35; http://dx.doi.org/10.1016/S0959-437X(98)80058-0; PMID: 9529602
   PubMed Web of Science ®Google Scholar
• Trimarchi JM, Lees JA. Sibling rivalry in the E2F family. Nat Rev Mol Cell Biol 2002; 3:11 - 20; http://dx.doi.org/10.1038/nrm714; PMID: 11823794
   PubMed Web of Science ®Google Scholar
• Bracken AP, Pasini D, Capra M, Prosperini E, Colli E, Helin K. EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer. EMBO J 2003; 22:5323 - 35; http://dx.doi.org/10.1093/emboj/cdg542; PMID: 14532106
   PubMed Web of Science ®Google Scholar
• Fujii S, Tokita K, Wada N, Ito K, Yamauchi C, Ito Y, et al. MEK-ERK pathway regulates EZH2 overexpression in association with aggressive breast cancer subtypes. Oncogene 2011; 30:4118 - 28; http://dx.doi.org/10.1038/onc.2011.118; PMID: 21499305
   PubMed Web of Science ®Google Scholar
• Chang CJ, Yang JY, Xia W, Chen CT, Xie X, Chao CH, et al. EZH2 promotes expansion of breast tumor initiating cells through activation of RAF1-β-catenin signaling. Cancer Cell 2011; 19:86 - 100; http://dx.doi.org/10.1016/j.ccr.2010.10.035; PMID: 21215703
   PubMed Web of Science ®Google Scholar
• Venkitaraman AR. Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell 2002; 108:171 - 82; http://dx.doi.org/10.1016/S0092-8674(02)00615-3; PMID: 11832208
   PubMed Web of Science ®Google Scholar
• Narod SA, Foulkes WD. BRCA1 and BRCA2: 1994 and beyond. Nat Rev Cancer 2004; 4:665 - 76; http://dx.doi.org/10.1038/nrc1431; PMID: 15343273
   PubMed Web of Science ®Google Scholar
• Wilson CA, Ramos L, Villaseñor MR, Anders KH, Press MF, Clarke K, et al. Localization of human BRCA1 and its loss in high-grade, non-inherited breast carcinomas. Nat Genet 1999; 21:236 - 40; http://dx.doi.org/10.1038/6029; PMID: 9988281
   PubMed Web of Science ®Google Scholar
• Turner NC, Reis-Filho JS, Russell AM, Springall RJ, Ryder K, Steele D, et al. BRCA1 dysfunction in sporadic basal-like breast cancer. Oncogene 2007; 26:2126 - 32; http://dx.doi.org/10.1038/sj.onc.1210014; PMID: 17016441
   PubMed Web of Science ®Google Scholar
• Foulkes WD, Stefansson IM, Chappuis PO, Bégin LR, Goffin JR, Wong N, et al. Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer. J Natl Cancer Inst 2003; 95:1482 - 5; http://dx.doi.org/10.1093/jnci/djg050; PMID: 14519755
   PubMed Web of Science ®Google Scholar
• Lakhani SR, Reis-Filho JS, Fulford L, Penault-Llorca F, van der Vijver M, Parry S, et al, Breast Cancer Linkage Consortium. Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype. Clin Cancer Res 2005; 11:5175 - 80; http://dx.doi.org/10.1158/1078-0432.CCR-04-2424; PMID: 16033833
   PubMed Web of Science ®Google Scholar
• Hervouet E, Cartron P-F, Jouvenot M, Delage-Mourroux R. Epigenetic regulation of estrogen signaling in breast cancer. Epigenetics 2013; 8:237 - 45; http://dx.doi.org/10.4161/epi.23790; PMID: 23364277
   PubMed Web of Science ®Google Scholar
• Hwang C, Giri VN, Wilkinson JC, Wright CW, Wilkinson AS, Cooney KA, et al. EZH2 regulates the transcription of estrogen-responsive genes through association with REA, an estrogen receptor corepressor. Breast Cancer Res Treat 2008; 107:235 - 42; http://dx.doi.org/10.1007/s10549-007-9542-7; PMID: 17453341
   PubMed Web of Science ®Google Scholar
• Schulz WA, Hoffmann MJ. Epigenetic mechanisms in the biology of prostate cancer. Semin Cancer Biol 2009; 19:172 - 80; http://dx.doi.org/10.1016/j.semcancer.2009.02.006; PMID: 19429481
   PubMed Web of Science ®Google Scholar
• Chen H, Tu SW, Hsieh JT. Down-regulation of human DAB2IP gene expression mediated by polycomb Ezh2 complex and histone deacetylase in prostate cancer. J Biol Chem 2005; 280:22437 - 44; http://dx.doi.org/10.1074/jbc.M501379200; PMID: 15817459
   PubMed Web of Science ®Google Scholar
• Beke L, Nuytten M, Van Eynde A, Beullens M, Bollen M. The gene encoding the prostatic tumor suppressor PSP94 is a target for repression by the Polycomb group protein EZH2. Oncogene 2007; 26:4590 - 5; http://dx.doi.org/10.1038/sj.onc.1210248; PMID: 17237810
   PubMed Web of Science ®Google Scholar
• Yu J, Cao Q, Yu J, Wu L, Dallol A, Li J, et al. The neuronal repellent SLIT2 is a target for repression by EZH2 in prostate cancer. Oncogene 2010; 29:5370 - 80; http://dx.doi.org/10.1038/onc.2010.269; PMID: 20622896
   PubMed Web of Science ®Google Scholar
• Cao Q, Yu J, Dhanasekaran SM, Kim JH, Mani RS, Tomlins SA, et al. Repression of E-cadherin by the polycomb group protein EZH2 in cancer. Oncogene 2008; 27:7274 - 84; http://dx.doi.org/10.1038/onc.2008.333; PMID: 18806826
   PubMed Web of Science ®Google Scholar
• Yu J, Cao Q, Mehra R, Laxman B, Yu J, Tomlins SA, et al. Integrative genomics analysis reveals silencing of beta-adrenergic signaling by polycomb in prostate cancer. Cancer Cell 2007; 12:419 - 31; http://dx.doi.org/10.1016/j.ccr.2007.10.016; PMID: 17996646
   PubMed Web of Science ®Google Scholar
• Shin YJ, Kim JH. The role of EZH2 in the regulation of the activity of matrix metalloproteinases in prostate cancer cells. PLoS One 2012; 7:e30393; http://dx.doi.org/10.1371/journal.pone.0030393; PMID: 22272343
   PubMedGoogle Scholar
• Yu J, Yu J, Rhodes DR, Tomlins SA, Cao X, Chen G, et al. A polycomb repression signature in metastatic prostate cancer predicts cancer outcome. Cancer Res 2007; 67:10657 - 63; http://dx.doi.org/10.1158/0008-5472.CAN-07-2498; PMID: 18006806
   PubMed Web of Science ®Google Scholar
• Yu J, Yu J, Mani RS, Cao Q, Brenner CJ, Cao X, et al. An integrated network of androgen receptor, polycomb, and TMPRSS2-ERG gene fusions in prostate cancer progression. Cancer Cell 2010; 17:443 - 54; http://dx.doi.org/10.1016/j.ccr.2010.03.018; PMID: 20478527
   PubMed Web of Science ®Google Scholar
• Shen MM, Abate-Shen C. Molecular genetics of prostate cancer: new prospects for old challenges. Genes Dev 2010; 24:1967 - 2000; http://dx.doi.org/10.1101/gad.1965810; PMID: 20844012
   PubMed Web of Science ®Google Scholar
• Bohrer LR, Chen S, Hallstrom TC, Huang H. Androgens suppress EZH2 expression via retinoblastoma (RB) and p130-dependent pathways: a potential mechanism of androgen-refractory progression of prostate cancer. Endocrinology 2010; 151:5136 - 45; http://dx.doi.org/10.1210/en.2010-0436; PMID: 20881251
   PubMed Web of Science ®Google Scholar
• Zhao JC, Yu J, Runkle C, Wu L, Hu M, Wu D, et al. Cooperation between Polycomb and androgen receptor during oncogenic transformation. Genome Res 2012; 22:322 - 31; http://dx.doi.org/10.1101/gr.131508.111; PMID: 22179855
   PubMed Web of Science ®Google Scholar
• Cai H, Memarzadeh S, Stoyanova T, Beharry Z, Kraft AS, Witte ON. Collaboration of Kras and androgen receptor signaling stimulates EZH2 expression and tumor-propagating cells in prostate cancer. Cancer Res 2012; 72:4672 - 81; http://dx.doi.org/10.1158/0008-5472.CAN-12-0228; PMID: 22805308
   PubMed Web of Science ®Google Scholar
• Chng KR, Chang CW, Tan SK, Yang C, Hong SZ, Sng NY, et al. A transcriptional repressor co-regulatory network governing androgen response in prostate cancers. EMBO J 2012; 31:2810 - 23; http://dx.doi.org/10.1038/emboj.2012.112; PMID: 22531786
   PubMed Web of Science ®Google Scholar
• Fujii S, Fukamachi K, Tsuda H, Ito K, Ito Y, Ochiai A. RAS oncogenic signal upregulates EZH2 in pancreatic cancer. Biochem Biophys Res Commun 2012; 417:1074 - 9; http://dx.doi.org/10.1016/j.bbrc.2011.12.099; PMID: 22222375
   PubMed Web of Science ®Google Scholar
• Borbone E, Troncone G, Ferraro A, Jasencakova Z, Stojic L, Esposito F, et al. Enhancer of zeste homolog 2 overexpression has a role in the development of anaplastic thyroid carcinomas. J Clin Endocrinol Metab 2011; 96:1029 - 38; http://dx.doi.org/10.1210/jc.2010-1784; PMID: 21289264
   PubMed Web of Science ®Google Scholar
• Cromer MK, Starker LF, Choi M, Udelsman R, Nelson-Williams C, Lifton RP, et al. Identification of somatic mutations in parathyroid tumors using whole-exome sequencing. J Clin Endocrinol Metab 2012; 97:E1774 - 81; http://dx.doi.org/10.1210/jc.2012-1743; PMID: 22740705
   PubMedGoogle Scholar
• Tan J, Yang X, Zhuang L, Jiang X, Chen W, Lee PL, et al. Pharmacologic disruption of Polycomb-repressive complex 2-mediated gene repression selectively induces apoptosis in cancer cells. Genes Dev 2007; 21:1050 - 63; http://dx.doi.org/10.1101/gad.1524107; PMID: 17437993
   PubMed Web of Science ®Google Scholar
• Miranda TB, Cortez CC, Yoo CB, Liang G, Abe M, Kelly TK, et al. DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation. Mol Cancer Ther 2009; 8:1579 - 88; http://dx.doi.org/10.1158/1535-7163.MCT-09-0013; PMID: 19509260
   PubMed Web of Science ®Google Scholar
• Crea F, Fornaro L, Bocci G, Sun L, Farrar WL, Falcone A, et al. EZH2 inhibition: targeting the crossroad of tumor invasion and angiogenesis. Cancer Metastasis Rev 2012; 31:753 - 61; http://dx.doi.org/10.1007/s10555-012-9387-3; PMID: 22711031
   PubMed Web of Science ®Google Scholar
• Knutson SK, Wigle TJ, Warholic NM, Sneeringer CJ, Allain CJ, Klaus CR, et al. A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells. Nat Chem Biol 2012; 8:890 - 6; PMID: 23023262
   PubMed Web of Science ®Google Scholar
• Qi W, Chan H, Teng L, Li L, Chuai S, Zhang R, et al. Selective inhibition of Ezh2 by a small molecule inhibitor blocks tumor cells proliferation. Proc Natl Acad Sci U S A 2012; 109:21360 - 5; http://dx.doi.org/10.1073/pnas.1210371110; PMID: 23236167
   PubMed Web of Science ®Google Scholar
• Dimri M, Bommi PV, Sahasrabuddhe AA, Khandekar JD, Dimri GP. Dietary omega-3 polyunsaturated fatty acids suppress expression of EZH2 in breast cancer cells. Carcinogenesis 2010; 31:489 - 95; http://dx.doi.org/10.1093/carcin/bgp305; PMID: 19969553
   PubMed Web of Science ®Google Scholar
• Hua W-F, Fu Y-S, Liao Y-J, Xia W-J, Chen Y-C, Zeng Y-X, et al. Curcumin induces down-regulation of EZH2 expression through the MAPK pathway in MDA-MB-435 human breast cancer cells. Eur J Pharmacol 2010; 637:16 - 21; http://dx.doi.org/10.1016/j.ejphar.2010.03.051; PMID: 20385124
   PubMed Web of Science ®Google Scholar
• Nandakumar V, Vaid M, Katiyar SK. (-)-Epigallocatechin-3-gallate reactivates silenced tumor suppressor genes, Cip1/p21 and p16INK4a, by reducing DNA methylation and increasing histones acetylation in human skin cancer cells. Carcinogenesis 2011; 32:537 - 44; http://dx.doi.org/10.1093/carcin/bgq285; PMID: 21209038
   PubMed Web of Science ®Google Scholar
• Kunderfranco P, Mello-Grand M, Cangemi R, Mensah A, Albertini V, et al. ETS transcription factors control transcription of EZH2 and epigenetic silencing of the tumor suppressor gene Nkx3.1 in prostate cancer.. PloS one 2010; 5:e10547
   PubMed Web of Science ®Google Scholar