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Cited by 1,649Epigenetics and DNA MethylationCancer Cells and MetastasisMechanisms of cancer metastasis

EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells

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Kleer, Celina G., Cao, Qi, Varambally, Sooryanarayana, Shen, Ronglai, Ota, Ichiro, Tomlins, Scott A., Ghosh, Debashis, Sewalt, Richard G. A. B. +7 more·2003·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1933744100PMC PMC208805
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Abstract

The Polycomb Group Protein EZH2 is a transcriptional repressor involved in controlling cellular memory and has been linked to aggressive prostate cancer. Here we investigate the functional role of EZH2 in cancer cell invasion and breast cancer progression. EZH2 transcript and protein were consistently elevated in invasive breast carcinoma compared with normal breast epithelia. Tissue microarray analysis, which included 917 samples from 280 patients, demonstrated that EZH2 protein levels were strongly associated with breast cancer aggressiveness. Overexpression of EZH2 in immortalized human mammary epithelial cell lines promotes anchorage-independent growth and cell invasion. EZH2-mediated cell invasion required an intact SET domain and histone deacetylase activity. This study provides compelling evidence for a functional link between dysregulated cellular memory, transcriptional repression, and neoplastic transformation.

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  • The increased response rates in EZH2-mutant tumours mirrors preclinical studies.

    “The increased response rates in EZH2-mutant tumours mirrors preclinical studies and highlights the importance of understanding the mechanisms underlying EZH2 dependence”

    From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [167]

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Authors
Kleer, C. G., Cao, Q., Varambally, S., Shen, R., Ota, I., Tomlins, S. A., Ghosh, D., Sewalt, R. G. A. B., Otte, A. P., Hayes, D. F., Sabel, M. S., Livant, D., Weiss, S. J., Rubin, M. A., & Chinnaiyan, A. M.
Affiliations
Brigham and Women's Hospital (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2003-09-19
Volume
100
Issue
20
Pages
11606-11611
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1933744100
PMC
PMC208805
OpenAlex
W2100365251
Cited by
1,649
References
38
Citations by year
2026: 21 · 2025: 43 · 2024: 53 · 2023: 72 · 2022: 55 · 2021: 67 · 2020: 94 · 2019: 69 · 2018: 83 · 2017: 91 · 2016: 109 · 2015: 109 · 2014: 116 · 2013: 114 · 2012: 108
FWCI
12.78
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • UvA-DARE (University of Amsterdam) (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Funders
National Cancer Institute (P50-CA-69568, R01CA097063, R01 CA97063, P50CA069568)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
Keywords
EZH2, Polycomb group proteins, breast cancer aggressiveness, breast cancer progression, cell invasion, anchorage-independent growth, oncogenic transformation, mammary epithelial cells, SET domain, histone deacetylase activity, transcriptional repression, cellular memory, prognostic factors
MeSH terms
Enhancer of Zeste Homolog 2 Protein, Breast, Breast Neoplasms, Cell Transformation, Neoplastic, DNA-Binding Proteins, Epithelial Cells, Female, Humans, Immunohistochemistry, Proteins, RNA, Messenger, Transcription Factors, Polymerase Chain Reaction, Polycomb Repressive Complex 2

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