Cited by 1,196Epigenetics and DNA MethylationCancer-related gene regulationGenomics and Chromatin Dynamics

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EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer.

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Bracken, Adrian P., Pasini, Diego, Capra, Maria, Prosperini, Elena, Colli, Elena, Helin, Kristian·2003·The EMBO Journal

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Abstract

Recent experiments have demonstrated that the Polycomb group (PcG) gene EZH2 is highly expressed in metastatic prostate cancer and in lymphomas. EZH2 is a component of the PRC2 histone methyltransferase complex, which also contains EED and SUZ12 and is required for the silencing of HOX gene expression during embryonic development. Here we demonstrate that both EZH2 and EED are essential for the proliferation of both transformed and non-transformed human cells. In addition, the pRB-E2F pathway tightly regulates their expression and, consistent with this, we find that EZH2 is highly expressed in a large set of human tumors. These results raise the question whether EZH2 is a marker of proliferation or if it is actually contributing to tumor formation. Significantly, we propose that EZH2 is a bona fide oncogene, since we find that ectopic expression of EZH2 is capable of providing a proliferative advantage to primary cells and, in addition, its gene locus is specifically amplified in several primary tumors.

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Hanahan, D., & Weinberg, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)81683-9 · Cited by 29,219
Tissue microarrays for high-throughput molecular profiling of tumor specimens
Kononen, J., Bubendorf, L., Kallionimeni, A., Barlund, M. T., Schraml, P., Leighton, S. B., Torhorst, J. K. H., Mihatsch, M. J., Sauter, G., & Kallionimeni, O.-P. (1998) · Nature Medicine · doi:10.1038/nm0798-844 · Cited by 4,101
Role of Histone H3 Lysine 27 Methylation in Polycomb-Group Silencing
Cao, R., Wang, L., Wang, H., Xia, L., Erdjument-Bromage, H., Tempst, P., Jones, R. S., & Zhang, Y. (2002) · Science · doi:10.1126/science.1076997 · Cited by 3,775
The polycomb group protein EZH2 is involved in progression of prostate cancer
Varambally, S., Dhanasekaran, S. M., Zhou, M., Barrette, T. R., Kumar-Sinha, C., Sanda, M. G., Ghosh, D., Pienta, K. J., Sewalt, R. G. A. B., Otte, A. P., et al. (2002) · Nature · doi:10.1038/nature01075 · Cited by 2,717
The regulation of E2F by pRB-family proteins.
Dyson, N. (1998) · Genes & Development · doi:10.1101/gad.12.15.2245 · Cited by 2,317
Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein
Kuzmichev, A., Nishioka, K., Erdjument-Bromage, H., Tempst, P., & Reinberg, D. (2002) · Genes & Development · doi:10.1101/gad.1035902 · Cited by 1,596
The oncogene and Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus
Jacobs, J. J. L., Kieboom, K., Marino, S., DePinho, R. A., & van Lohuizen, M. (1999) · Nature · doi:10.1038/16476 · Cited by 1,580
Histone Methyltransferase Activity of a Drosophila Polycomb Group Repressor Complex
Müller, J., Hart, C. M., Francis, N. J., Vargas, M. L., Sengupta, A. K., Wild, B., Miller, E., O’Connor, M. B., Kingston, R. E., & Simon, J. A. (2002) · Cell · doi:10.1016/s0092-8674(02)00976-5 · Cited by 1,553
Drosophila Enhancer of Zeste/ESC Complexes Have a Histone H3 Methyltransferase Activity that Marks Chromosomal Polycomb Sites
Czermin, B., Melfi, R., McCabe, D., Seitz, V., Imhof, A., & Pirrotta, V. (2002) · Cell · doi:10.1016/s0092-8674(02)00975-3 · Cited by 1,536
Microarray analysis reveals a major direct role of DNA copy number alteration in the transcriptional program of human breast tumors
Pollack, J. R., Sørlie, T., Perou, C. M., Rees, C. A., Jeffrey, S. S., Lønning, P. E., Tibshirani, R. J., Botstein, D., Børresen‐Dale, A., & Brown, P. O. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.162471999 · Cited by 1,167

Show all 43 references

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Wu, G.-Q., Chai, K.-Q., Zhu, X.-M., Jiang, H., Wang, X., Xue, Q., Zheng, A.-H., Zhou, H.-Y., Chen, Y., Chen, X.-C., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.8532 · Cited by 98
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Li, H., Li, J., Jia, S., Wu, M., An, J., Zheng, Q., Zhang, W., & Lu, D. (2015) · Oncotarget · doi:10.18632/oncotarget.5579 · Cited by 94
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Sheikh, B. N., Phipson, B., El-Saafin, F., Vanyai, H. K., Downer, N. L., Bird, M., Kueh, A. J., May, R. E., Smyth, G. K., Voss, A. K., et al. (2015) · Oncogene · doi:10.1038/onc.2015.33 · Cited by 96
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Wigle, T. J., Knutson, S. K., Jin, L., Kuntz, K. W., Pollock, R. M., Richon, V. M., Copeland, R. A., & Scott, M. P. (2011) · FEBS Letters · doi:10.1016/j.febslet.2011.08.018 · Cited by 94
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Wu, Z., Lee, S. T., Qiao, Y., Li, Z., Lee, P. L., Lee, Y. J., Jiang, X., Tan, J. Y., Aau, M., Lim, C. Z. H., et al. (2011) · Cell Death and Differentiation · doi:10.1038/cdd.2011.48 · Cited by 95
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Du, J., Li, L., Ou, Z., Kong, C., Zhang, Y., Dong, Z., Zhu, S., Jiang, H., Shao, Z., Huang, B., et al. (2011) · Breast Cancer Research and Treatment · doi:10.1007/s10549-011-1396-3 · Cited by 90
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Engelsen, I. B., Akslen, L. A., & Salvesen, H. B. (2009) · Apmis · doi:10.1111/j.1600-0463.2009.02467.x · Cited by 85
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“, 2010), and wild-type EZH2 is commonly overexpressed in a variety of cancers (Bracken et al., 2003), only one report of EZH2 overexpression in MDS exists (Xu et al.”
Background
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Zhang, Y., Chen, J., Lian, H., Pei, J., Li, Y., Chen, X., Song, S., Xia, J., Zhou, B., Feng, J., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.06.065 · Cited by 80
MiRNAs, epigenetics, and cancer
ROUHI, A. M., Mager, D. L., Humphries, R. K., & Kuchenbauer, F. C. (2008) · Mammalian Genome · doi:10.1007/s00335-008-9133-x · Cited by 82
Heterochromatin protein 1α: a hallmark of cell proliferation relevant to clinical oncology
de Koning, L., Savignoni, A., Boumendil, C., Rehman, H., Asselain, B. J. R., Sastre‐Garau, X., & Almouzni, G. (2009) · EMBO Molecular Medicine · doi:10.1002/emmm.200900022 · Cited by 80
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Schulz, W. A., & Hoffmann, M. J. (2009) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2009.02.006 · Cited by 79
Transcriptional Regulation of Arabidopsis Polycomb Repressive Complex 2 Coordinates Cell-Type Proliferation and Differentiation
de Lucas, M., Pu, L., Turco, G. M., Gaudinier, A., Morao, A. K., Harashima, H., Kim, D., Ron, M., Sugimoto, K., Roudier, F., et al. (2016) · The Plant Cell · doi:10.1105/tpc.15.00744 · Cited by 84
Replicating nucleosomes
Ramachandran, S., & Henikoff, S. (2015) · Science Advances · doi:10.1126/sciadv.1500587 · Cited by 78
Chromatin-modifying enzymes as therapeutic targets – Part 1
Keppler, B. R., & Archer, T. (2008) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.12.10.1301 · Cited by 89
O s FIE 2 plays an essential role in the regulation of rice vegetative and reproductive development
Li, S., Zhou, B., Peng, X., Kuang, Q., Huang, X., Yao, J., Du, B., & Sun, M. (2013) · New Phytologist · doi:10.1111/nph.12472 · Cited by 78
The polycomb group protein EZH2 is a novel therapeutic target in tongue cancer
Li, Z., Wang, Y., Qiu, J., Li, Q., Yuan, C., Zhang, W., Wang, D., Ye, J., Jiang, H., Yang, J., et al. (2013) · Oncotarget · doi:10.18632/oncotarget.1503 · Cited by 79
Curcumin inhibits invasive capabilities through epithelial mesenchymal transition in breast cancer cell lines
Gallardo, M., & Calaf, G. M. (2016) · International Journal of Oncology · doi:10.3892/ijo.2016.3598 · Cited by 78
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Mathews, L., Crea, F., & Farrar, W. L. (2009) · Differentiation · doi:10.1016/j.diff.2009.04.002 · Cited by 79
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Nuytten, M., Beke, L., Eynde, A. V., Ceulemans, H., Beullens, M., Hummelen, P. V., Fuks, F., & Bollen, M. (2007) · Oncogene · doi:10.1038/sj.onc.1210774 · Cited by 86
Making Sense of the Epigenome Using Data Integration Approaches
Cazaly, E., Saad, J. J., Wang, W., Heckman, C. A., Ollikainen, M., & Tang, J. P. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00126 · Cited by 77
Finding an easy way to harmonize: a review of advances in clinical research and combination strategies of EZH2 inhibitors
Li, C., Wang, Y., Gong, Y., Zhang, T., Huang, J., Tan, Z. W., & Xue, L. (2021) · Clinical Epigenetics · doi:10.1186/s13148-021-01045-1 · Cited by 82
Importance of Ezh2 polycomb protein in tumorigenesis process interfering with the pathway of growth suppressive key elements
Tonini, T., D’Andrilli, G., Fucito, A., Gaspa, L., & Bagella, L. (2007) · Journal of Cellular Physiology · doi:10.1002/jcp.21241 · Cited by 75
Mechanisms of Yin Yang 1 in Oncogenesis: The Importance of Indirect Effects
Atchison, M. L., Basu, A., Zápražná, K., & Papasani, M. R. (2011) · Critical Reviews™ in Oncogenesis · doi:10.1615/critrevoncog.v16.i3-4.20 · Cited by 74
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He, M., Zhang, W., Bakken, T., Schutten, M. M., Tóth, Z., Jung, J. U., Gill, P. S., Cannon, M., & Gao, S. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-2876 · Cited by 78
VEGF/VEGFR-2 Upregulates EZH2 Expression in Lung Adenocarcinoma Cells and EZH2 Depletion Enhances the Response to Platinum-Based and VEGFR-2–Targeted Therapy
Riquelme, E. M., Suraokar, M. B., Behrens, C., Lin, H. Y., Girard, L., Nilsson, M. B., Simon, G. R., Wang, J., Coombes, K. R., Lee, J. J., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-1916 · Cited by 77
Inhibition of EZH2 reverses chemotherapeutic drug TMZ chemosensitivity in glioblastoma.
Fan, T.-Y., Wang, H., Peng, X., Liu, Y., Li, H., Lei, B., Yu, M., & Qi, S. (2014) · PubMed Central · Cited by 76
EZH2 Modifies Sunitinib Resistance in Renal Cell Carcinoma by Kinome Reprogramming
Adelaiye-Ogala, R. M., Budka, J. A., Damayanti, N. P., Arrington, J. V., Ferris, M. W., Hsu, C.-C., Chintala, S., Orillion, A. R., Miles, K. M., Shen, L., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-0899 · Cited by 78
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Park, S. H., Fong, K.-W., Kim, J., Wang, F., Lü, X., Lee, Y., Brea, L. T., Wadosky, K. M., Guo, C., Abdulkadir, S. A., et al. (2021) · Science Advances · doi:10.1126/sciadv.abe2261 · Cited by 78
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SILAC-based proteomic analysis to dissect the “histone modification signature” of human breast cancer cells
Cuomo, A., Moretti, S., Minucci, S., & Bonaldi, T. (2010) · Amino Acids · doi:10.1007/s00726-010-0668-2 · Cited by 79
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Bohrer, L. R., Chen, D., Hallstrom, T. C., & Huang, H. (2010) · Endocrinology · doi:10.1210/en.2010-0436 · Cited by 76
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Chang, Y., Ding, B., Zhang, X., Deng, X., Deng, K., Cheng, Z., Xing, B., Jin, D., Ma, P., & Lin, J. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.11.014 · Cited by 76
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Poli, V., Fagnocchi, L., & Zippo, A. (2018) · Stem Cells International · doi:10.1155/2018/4598195 · Cited by 81
Polycomb group protein gene silencing, non-coding RNA, stem cells, and cancerThis paper is one of a selection of papers published in this Special Issue, entitled The 30th Annual International Asilomar Chromatin and Chromosomes Conference, and has undergone the Journal's usual peer review process.
Gieni, R. S., & Hendzel, M. J. (2009) · Biochemistry and Cell Biology · doi:10.1139/o09-057 · Cited by 76
Malignant Peripheral Nerve Sheath Tumors: From Epigenome to Bedside
Korfhage, J. L., & Lombard, D. B. (2019) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-19-0147 · Cited by 78
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Borbone, E., Troncone, G., Ferraro, A., Jasencakova, Z., Stojic, L., Esposito, F., Hornig, N., Fusco, A., & Orlando, V. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-1784 · Cited by 77
Polycomb repressive complex’s evolutionary conserved function: the role of EZH2 status and cellular background
Gall‐Tros̆elj, K., Kujundžić, R. N., & Ugarkovic, D. (2016) · Clinical Epigenetics · doi:10.1186/s13148-016-0226-1 · Cited by 73
Tanshinone I, a new EZH2 inhibitor restricts normal and malignant hematopoiesis through upregulation of MMP9 and ABCG2
Huang, Y., Yu, S., Zhen, W., Cheng, T., Wang, D., Lin, J., Wu, Y., Wang, Y., Chen, Y., Shu, L., et al. (2021) · Theranostics · doi:10.7150/thno.53170 · Cited by 74
Epigenetic Factors in Cancer Development: Polycomb Group Proteins
Piunti, A., & Pasini, D. (2010) · Future Oncology · doi:10.2217/fon.10.157 · Cited by 76
Self-citation
New anti-cancer strategies: Epigenetic therapies and biomarkers
Balch, C. (2005) · Frontiers in bioscience · doi:10.2741/1668 · Cited by 74

Authors: Bracken, A. P., Pasini, D., Capra, M., Prosperini, E., Colli, E., & Helin, K.
Affiliations: European Institute of Oncology (IT)
IFOM (IT)
Corresponding author: Helin, Kristian
ORCID: Bracken, Adrian P.
Pasini, Diego
Helin, Kristian
Venue: The EMBO Journal
Publisher: Springer Science and Business Media LLC
Published: 2003-10-15
Volume: 22
Issue: 20
Pages: 5323-5335
ISSN: 0261-4189 (ISSN-L)
1460-2075
DOI: 10.1093/emboj/cdg542
PMC: PMC213796
OpenAlex: W2171439874
Cited by: 1,196
References: 43
Citations by year: 2026: 16 · 2025: 33 · 2024: 39 · 2023: 52 · 2022: 35 · 2021: 64 · 2020: 66 · 2019: 56 · 2018: 53 · 2017: 65 · 2016: 74 · 2015: 63 · 2014: 65 · 2013: 61 · 2012: 58
FWCI: 11.03
Type: journal article
Language: en
Update notices: correction (2024-02-12)
Open access: green
europepmc.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: The EMBO Journal (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
RePEc: Research Papers in Economics (submittedVersion)
Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders: European Commission
Associazione Italiana per la Ricerca sul Cancro
Fondazione Italiana per la Ricerca sul Cancro
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords: EZH2, Polycomb group genes, polycomb repressive complex 2, EED, oncogenes, cell proliferation, gene amplification, prostate cancer, lymphoma, histone methyltransferase, tumor formation
MeSH terms: Enhancer of Zeste Homolog 2 Protein, Animals, Base Sequence, Cell Division, Cell Line, DNA-Binding Proteins, Gene Amplification, Genetic Markers, Humans, Kinetics, Lymphoma, Male, Oncogenes, Promoter Regions, Genetic, Prostatic Neoplasms, Proteins, Recombinant Proteins, Transcription Factors, Transfection, Transcriptional Activation, Retinoblastoma Protein, DNA Primers, Cell Cycle Proteins, E2F Transcription Factors, Rats, Polycomb Repressive Complex 2

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EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer.

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