The polycomb group protein EZH2 is involved in progression of prostate cancer
Open accessAbstract
Prostate cancer is a leading cause of cancer-related death in males and is second only to lung cancer. Although effective surgical and radiation treatments exist for clinically localized prostate cancer, metastatic prostate cancer remains essentially incurable. Here we show, through gene expression profiling, that the polycomb group protein enhancer of zeste homolog 2 (EZH2) is overexpressed in hormone-refractory, metastatic prostate cancer. Small interfering RNA (siRNA) duplexes targeted against EZH2 reduce the amounts of EZH2 protein present in prostate cells and also inhibit cell proliferation in vitro. Ectopic expression of EZH2 in prostate cells induces transcriptional repression of a specific cohort of genes. Gene silencing mediated by EZH2 requires the SET domain and is attenuated by inhibiting histone deacetylase activity. Amounts of both EZH2 messenger RNA and EZH2 protein are increased in metastatic prostate cancer; in addition, clinically localized prostate cancers that express higher concentrations of EZH2 show a poorer prognosis. Thus, dysregulated expression of EZH2 may be involved in the progression of prostate cancer, as well as being a marker that distinguishes indolent prostate cancer from those at risk of lethal progression.
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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 [168]
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- Authors
- 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., Rubin, M. A., & Chinnaiyan, A. M.
- Affiliations
- University of Michigan (US)
- University of Amsterdam (NL)
- Corresponding author
- Chinnaiyan, Arul M.
- ORCID
- Venue
- Nature
- Published
- 2002-10
- Volume
- 419
- Issue
- 6907
- Pages
- 624-629
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1996487270
- Cited by
- 2,717
- References
- 29
- Citations by year
- 2026: 54 · 2025: 61 · 2024: 87 · 2023: 140 · 2022: 102 · 2021: 129 · 2020: 120 · 2019: 106 · 2018: 118 · 2017: 130 · 2016: 162 · 2015: 138 · 2014: 161 · 2013: 148 · 2012: 155
- FWCI
- 67.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- UvA-DARE (University of Amsterdam) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- University of Michigan
- National Institutes of Health
- National Cancer Institute
- National Institute of General Medical Sciences
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- 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
- Keywords
- EZH2, Polycomb group proteins, prostate cancer, metastatic prostate cancer, castration-resistant prostate cancer, SET domain, histone deacetylase, transcriptional repression, gene silencing, cell proliferation, prognostic factors, tumor progression, gene expression profiling
- MeSH terms
- Humans, Male, Molecular Sequence Data, Nuclear Proteins, Phenotype, Predictive Value of Tests, Prostatic Neoplasms, Repressor Proteins, RNA, Messenger, Transfection, Tumor Cells, Cultured, Biomarkers, Tumor, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, Treatment Outcome, Disease Progression, Oligonucleotide Array Sequence Analysis, Gene Silencing, Gene Expression Profiling, Drosophila Proteins, RNA, Small Interfering, Polycomb Repressive Complex 2
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