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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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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