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

Sooryanarayana Varambally, Saravana M. Dhanasekaran, Ming Zhou, Terrence R. Barrette, Chandan Kumar-Sinha, Martin G. Sanda, Debashis Ghosh, Kenneth Pienta, Richard G A B Sewalt, Arie P. Otte, Mark A. Rubin, Arul M. Chinnaiyan

Research output: Contribution to journalArticle

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 profiling, that the polycomb group protein enhancer of zeste homolog 2 (EZH2) is over-expressed 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.

Original languageEnglish (US)
Pages (from-to)624-629
Number of pages6
JournalNature
Volume419
Issue number6907
DOIs
StatePublished - Oct 10 2002
Externally publishedYes

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Polycomb-Group Proteins
Prostatic Neoplasms
Prostate
Enhancer of Zeste Homolog 2 Protein
Histone Deacetylases
Gene Silencing
Gene Expression Profiling
Small Interfering RNA
Lung Neoplasms
Cell Proliferation
Hormones
Radiation

ASJC Scopus subject areas

  • General

Cite this

Varambally, S., Dhanasekaran, S. M., Zhou, M., Barrette, T. R., Kumar-Sinha, C., Sanda, M. G., ... Chinnaiyan, A. M. (2002). The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature, 419(6907), 624-629. https://doi.org/10.1038/nature01075

The polycomb group protein EZH2 is involved in progression of prostate cancer. / Varambally, Sooryanarayana; Dhanasekaran, Saravana M.; Zhou, Ming; Barrette, Terrence R.; Kumar-Sinha, Chandan; Sanda, Martin G.; Ghosh, Debashis; Pienta, Kenneth; Sewalt, Richard G A B; Otte, Arie P.; Rubin, Mark A.; Chinnaiyan, Arul M.

In: Nature, Vol. 419, No. 6907, 10.10.2002, p. 624-629.

Research output: Contribution to journalArticle

Varambally, S, Dhanasekaran, SM, Zhou, M, Barrette, TR, Kumar-Sinha, C, Sanda, MG, Ghosh, D, Pienta, K, Sewalt, RGAB, Otte, AP, Rubin, MA & Chinnaiyan, AM 2002, 'The polycomb group protein EZH2 is involved in progression of prostate cancer', Nature, vol. 419, no. 6907, pp. 624-629. https://doi.org/10.1038/nature01075
Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar-Sinha C, Sanda MG et al. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature. 2002 Oct 10;419(6907):624-629. https://doi.org/10.1038/nature01075
Varambally, Sooryanarayana ; Dhanasekaran, Saravana M. ; Zhou, Ming ; Barrette, Terrence R. ; Kumar-Sinha, Chandan ; Sanda, Martin G. ; Ghosh, Debashis ; Pienta, Kenneth ; Sewalt, Richard G A B ; Otte, Arie P. ; Rubin, Mark A. ; Chinnaiyan, Arul M. / The polycomb group protein EZH2 is involved in progression of prostate cancer. In: Nature. 2002 ; Vol. 419, No. 6907. pp. 624-629.
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AB - 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 over-expressed 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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