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

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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., Otte, Arie P., Hayes, Daniel F., Sabel, Michael S., Livant, Donna, Weiss, Stephen J., Rubin, Mark A., Chinnaiyan, Arul M.·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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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: Kleer, Celina G.
Cao, Qi
Varambally, Sooryanarayana
Shen, Ronglai
Ota, Ichiro
Tomlins, Scott A.
Hayes, Daniel F.
Sabel, Michael S.
Weiss, Stephen J.
Rubin, Mark A.
Chinnaiyan, Arul M.
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: green
www.ncbi.nlm.nih.gov
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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EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells

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