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The polycomb group protein EZH2 is involved in progression of prostate cancer

Author

Listed:
  • Sooryanarayana Varambally

    (University of Michigan Medical School)

  • Saravana M. Dhanasekaran

    (University of Michigan Medical School)

  • Ming Zhou

    (University of Michigan Medical School)

  • Terrence R. Barrette

    (University of Michigan Medical School)

  • Chandan Kumar-Sinha

    (University of Michigan Medical School)

  • Martin G. Sanda

    (University of Michigan Medical School
    University of Michigan Medical School)

  • Debashis Ghosh

    (University of Michigan Medical School)

  • Kenneth J. Pienta

    (University of Michigan Medical School
    University of Michigan Medical School
    University of Michigan Medical School)

  • Richard G. A. B. Sewalt

    (University of Amsterdam)

  • Arie P. Otte

    (University of Amsterdam)

  • Mark A. Rubin

    (University of Michigan Medical School
    University of Michigan Medical School
    University of Michigan Medical School)

  • Arul M. Chinnaiyan

    (University of Michigan Medical School
    University of Michigan Medical School
    University of Michigan Medical School)

Abstract

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 profiling1, that the polycomb group protein enhancer of zeste homolog 2 (EZH2)2,3 is overexpressed in hormone-refractory, metastatic prostate cancer. Small interfering RNA (siRNA) duplexes4 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.

Suggested Citation

  • Sooryanarayana Varambally & Saravana M. Dhanasekaran & Ming Zhou & Terrence R. Barrette & Chandan Kumar-Sinha & Martin G. Sanda & Debashis Ghosh & Kenneth J. Pienta & Richard G. A. B. Sewalt & Arie P., 2002. "The polycomb group protein EZH2 is involved in progression of prostate cancer," Nature, Nature, vol. 419(6907), pages 624-629, October.
    • Handle: RePEc:nat:nature:v:419:y:2002:i:6907:d:10.1038_nature01075
    DOI: 10.1038/nature01075
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    Cited by:

    1. Ayushi Verma & Akhilesh Singh & Manish Pratap Singh & Mushtaq Ahmad Nengroo & Krishan Kumar Saini & Saumya Ranjan Satrusal & Muqtada Ali Khan & Priyank Chaturvedi & Abhipsa Sinha & Sanjeev Meena & Anu, 2022. "EZH2-H3K27me3 mediated KRT14 upregulation promotes TNBC peritoneal metastasis," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    2. Debashis Ghosh & Arul Chinnaiyan, 2004. "Covariate adjustment in the analysis of microarray data from clinical studies," The University of Michigan Department of Biostatistics Working Paper Series 1030, Berkeley Electronic Press.
    3. Nishit Goradia & Stefan Werner & Edukondalu Mullapudi & Sarah Greimeier & Lina Bergmann & Andras Lang & Haydyn Mertens & Aleksandra Węglarz & Simon Sander & Grzegorz Chojnowski & Harriet Wikman & Oliv, 2024. "Master corepressor inactivation through multivalent SLiM-induced polymerization mediated by the oncogene suppressor RAI2," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. Shengrui Feng & Sajid A. Marhon & Dustin J. Sokolowski & Alister D’Costa & Fraser Soares & Parinaz Mehdipour & Charles Ishak & Helen Loo Yau & Ilias Ettayebi & Parasvi S. Patel & Raymond Chen & Jiming, 2024. "Inhibiting EZH2 targets atypical teratoid rhabdoid tumor by triggering viral mimicry via both RNA and DNA sensing pathways," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    5. Jiwei Zhao, 2017. "Reducing bias for maximum approximate conditional likelihood estimator with general missing data mechanism," Journal of Nonparametric Statistics, Taylor & Francis Journals, vol. 29(3), pages 577-593, July.
    6. Marco Bolis & Daniela Bossi & Arianna Vallerga & Valentina Ceserani & Manuela Cavalli & Daniela Impellizzieri & Laura Di Rito & Eugenio Zoni & Simone Mosole & Angela Rita Elia & Andrea Rinaldi & Ricar, 2021. "Dynamic prostate cancer transcriptome analysis delineates the trajectory to disease progression," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    7. Antonio Rodriguez-Calero & John Gallon & Dilara Akhoundova & Sina Maletti & Alison Ferguson & Joanna Cyrta & Ursula Amstutz & Andrea Garofoli & Viola Paradiso & Scott A. Tomlins & Ekkehard Hewer & Ver, 2022. "Alterations in homologous recombination repair genes in prostate cancer brain metastases," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    8. Yatian Li & Zhenyue Gao & Yuhong Wang & Bo Pang & Binbin Zhang & Ruxin Hu & Yuqing Wang & Chao Liu & Xuebin Zhang & Jingxuan Yang & Mei Mei & Yongzhi Wang & Xuan Zhou & Min Li & Yu Ren, 2023. "Lysine methylation promotes NFAT5 activation and determines temozolomide efficacy in glioblastoma," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    9. Tian Tian & Chunjian Li & Jing Xiao & Yi Shen & Yihua Lu & Liying Jiang & Xun Zhuang & Minjie Chu, 2016. "Quantitative Assessment of the Polymorphisms in the HOTAIR lncRNA and Cancer Risk: A Meta-Analysis of 8 Case-Control Studies," PLOS ONE, Public Library of Science, vol. 11(3), pages 1-11, March.

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