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

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Foster, C. S., Falconer, A., Dodson, A. R., Norman, A. R., Dennis, N. M., Fletcher, A., Southgate, C., Dowe, A., Dearnaley, D. P., Jhavar, S. G., et al. (2004) · Oncogene · doi:10.1038/sj.onc.1207800 · Cited by 154
BAZ2A (TIP5) is involved in epigenetic alterations in prostate cancer and its overexpression predicts disease recurrence
ICGC Project on Early Onset Prostate Cancer, Gu, L., Frommel, S. C., Oakes, C. C., Simon, R., Grupp, K., Gerig, C. Y., Bär, D., Robinson, M. D., Baer, C. R., et al. (2014) · Nature Genetics · doi:10.1038/ng.3165 · Cited by 154
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Bernard, D., Martínez-Leal, J. F., Rizzo, S., Martínez, D., Hudson, D. L., Visakorpi, T., Peters, G. G., Carnero, A., Beach, D., & Gil, J. (2005) · Oncogene · doi:10.1038/sj.onc.1208735 · Cited by 149
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Majer, C. R., Jin, L., Scott, M. P., Knutson, S. K., Kuntz, K. W., Keilhack, H., Smith, J. J., Moyer, M. P., Richon, V. M., Copeland, R. A., et al. (2012) · FEBS Letters · doi:10.1016/j.febslet.2012.07.066 · Cited by 154
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for the Norwegian Gastrointestinal Cancer Group, Fluge, Ø., Gravdal, K., Carlsen, E., Vonen, B., Kjellevold, K. H., Refsum, S. B., Lilleng, R., Eide, T. J., Halvorsen, T. B., et al. (2009) · British Journal of Cancer · doi:10.1038/sj.bjc.6605333 · Cited by 147
EZH2, an epigenetic driver of prostate cancer
Yang, Y. A., & Yu, J. (2013) · Protein & Cell · doi:10.1007/s13238-013-2093-2 · Cited by 153
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Coppola, V., Maria, R. D., & Bonci, D. (2009) · Endocrine Related Cancer · doi:10.1677/erc-09-0172 · Cited by 152
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Rao, Z.-Y., Cai, M.-Y., Yang, G.-F., He, L.-R., Mai, S., Hua, W., Liao, Y.-J., Deng, H.-X., Chen, Y., Guan, X., et al. (2010) · Carcinogenesis · doi:10.1093/carcin/bgq150 · Cited by 152
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Nowak, K. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl119 · Cited by 149
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Kalari, S. K., & Pfeifer, G. P. (2010) · Advances in genetics · doi:10.1016/b978-0-12-380866-0.60010-1 · Cited by 143
Coupling cell proliferation and development in plants
Gutiérrez, C. (2005) · Nature Cell Biology · doi:10.1038/ncb0605-535 · Cited by 144
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Wang, J. K., Tsai, M.-C., Poulin, G. B., Adler, A. S., Chen, S., Liu, H., Shi, Y., & Chang, H. Y. (2010) · Genes & Development · doi:10.1101/gad.1882610 · Cited by 152
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Wan, J., Zhan, J., Li, S., Ma, J., Xu, W., Liu, C., Xue, X., Xie, Y., Fang, W., Chin, Y. E., et al. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv238 · Cited by 143
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Zirn, B., Hartmann, O., Samans, B., Krause, M., Wittmann, S., Mertens, F., Graf, N. M., Eilers, M., & Gessler, M. (2005) · International Journal of Cancer · doi:10.1002/ijc.21564 · Cited by 102
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Zeidler, M. G., Varambally, S., Cao, Q., Chinnaiyan, A. M., Ferguson, D. O., Merajver, S. D., & Kleer, C. G. (2005) · Neoplasia · doi:10.1593/neo.05472 · Cited by 105

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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