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Breast Cancer Research
Published in: Breast Cancer Research 3/2011

01-06-2011 | Viewpoint

EZH2-mediated epigenetic repression of DNA repair in promoting breast tumor initiating cells

Authors: Olafur Andri Stefansson, Manel Esteller

Published in: Breast Cancer Research | Issue 3/2011

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Abstract

Members of the Polycomb-group (PcG) family of proteins, including EZH2 (enhancer of zeste homolog 2), are involved in establishing epigenetic silencing of developmental genes in adult and embryonic stem cells, and their deregulation has been implicated in cancer. In a recent report, EZH2-mediated epigenetic repression of DNA damage repair in breast tumor initiating cells (BTICs) was identified as a mechanism that could promote expansion of BTICs, and may contribute to cancer progression.
Literature
1.
Simon JA, Lange CA: Roles of the EZH2 histone methyltransferase in cancer epigenetics. Mutat Res. 2008, 647: 21-29.CrossRefPubMed
2.
Pasini D, Bracken AP, Hansen JB, Capillo M, Helin K: The polycomb group protein Suz12 is required for embryonic stem cell differentiation. Mol Cell Biol. 2007, 27: 3769-3779. 10.1128/MCB.01432-06.CrossRefPubMedPubMedCentral
3.
Lee TI, Jenner RG, Boyer LA, Guenther MG, Levine SS, Kumar RM, Chevalier B, Johnstone SE, Cole MF, Isono K, Koseki H, Fuchikami T, Abe K, Murray HL, Zucker JP, Yuan B, Bell GW, Herbolsheimer E, Hannett NM, Sun K, Odom DT, Otte AP, Volkert TL, Bartel DP, Melton DA, Gifford DK, Jaenisch R, Young RA: Control of developmental regulators by Polycomb in human embryonic stem cells. Cell. 2006, 125: 301-313. 10.1016/j.cell.2006.02.043.CrossRefPubMedPubMedCentral
4.
Rajasekhar VK, Begemann M: Concise review: roles of polycomb group proteins in development and disease: a stem cell perspective. Stem Cells. 2007, 25: 2498-2510. 10.1634/stemcells.2006-0608.CrossRefPubMed
5.
Huang TH, Esteller M: Chromatin remodeling in mammary gland differentiation and breast tumorigenesis. Cold Spring Harb Perspect Biol. 2010, 2: a004515-10.1101/cshperspect.a004515.PubMedPubMedCentral
6.
Clevers H: The cancer stem cell: premises, promises and challenges. Nat Med. 2011, 17: 313-319. 10.1038/nsmb.1756.CrossRefPubMed
7.
Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF: Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 2003, 100: 3983-3988. 10.1073/pnas.0530291100.CrossRefPubMedPubMedCentral
8.
Chang CJ, Yang JY, Xia W, Chen CT, Xie X, Chao CH, Woodward WA, Hsu JM, Hortobagyi GN, Hung MC: EZH2 promotes expansion of breast tumor initiating cells through activation of RAF1-beta-catenin signaling. Cancer Cell. 2011, 19: 86-100. 10.1016/j.ccr.2010.10.035.CrossRefPubMedPubMedCentral
9.
Kleer CG, Cao Q, Varambally S, Shen R, Ota I, Tomlins SA, Ghosh D, Sewalt RG, Otte AP, Hayes DF, Sabel MS, Livant D, Weiss SJ, Rubin MA, Chinnaiyan AM: EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc Natl Acad Sci USA. 2003, 100: 11606-11611. 10.1073/pnas.1933744100.CrossRefPubMedPubMedCentral
10.
Zeidler M, Varambally S, Cao Q, Chinnaiyan AM, Ferguson DO, Merajver SD, Kleer CG: The Polycomb group protein EZH2 impairs DNA repair in breast epithelial cells. Neoplasia. 2005, 7: 1011-1019. 10.1593/neo.05472.CrossRefPubMedPubMedCentral
11.
McCabe N, Turner NC, Lord CJ, Kluzek K, Bialkowska A, Swift S, Giavara S, O'Connor MJ, Tutt AN, Zdzienicka MZ, Smith GC, Ashworth A: Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition. Cancer Res. 2006, 66: 8109-8115. 10.1158/0008-5472.CAN-06-0140.CrossRefPubMed
12.
Negrini S, Gorgoulis VG, Halazonetis TD: Genomic instability - an evolving hallmark of cancer. Nat Rev Mol Cell Biol. 2010, 11: 220-228. 10.1038/nrm2858.CrossRefPubMed
13.
Esteller M: Epigenetic lesions causing genetic lesions in human cancer: promoter hypermethylation of DNA repair genes. Eur J Cancer. 2000, 36: 2294-2300. 10.1016/S0959-8049(00)00303-8.CrossRefPubMed
14.
Esteller M, Silva JM, Dominguez G, Bonilla F, Matias-Guiu X, Lerma E, Bussaglia E, Prat J, Harkes IC, Repasky EA, Gabrielson E, Schutte M, Baylin SB, Herman JG: Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors. J Natl Cancer Inst. 2000, 92: 564-569. 10.1093/jnci/92.7.564.CrossRefPubMed
15.
Birgisdottir V, Stefansson OA, Bodvarsdottir SK, Hilmarsdottir H, Jonasson JG, Eyfj ord JE: Epigenetic silencing and deletion of the BRCA1 gene in sporadic breast cancer. Breast Cancer Res. 2006, 8: R38-10.1186/bcr1522.CrossRefPubMedPubMedCentral
16.
Murphy CG, Moynahan ME: BRCA gene structure and function in tumor suppression: a repair-centric perspective. Cancer J. 2010, 16: 39-47. 10.1097/PPO.0b013e3181cf0204.CrossRefPubMed
17.
Lim E, Vaillant F, Wu D, Forrest NC, Pal B, Hart AH, Asselin-Labat ML, Gyorki DE, Ward T, Partanen A, Feleppa F, Huschtscha LI, Thorne HJ, kConFab, Fox SB, Yan M, French JD, Brown MA, Smyth GK, Visvader JE, Lindeman GJ: Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers. Nat Med. 2009, 15: 907-913. 10.1038/nm.2000.CrossRefPubMed
Metadata
Title
EZH2-mediated epigenetic repression of DNA repair in promoting breast tumor initiating cells
Authors
Olafur Andri Stefansson
Manel Esteller
Publication date
01-06-2011
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 3/2011
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr2871

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