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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2002-10

AUTHORS

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. Otte, Mark A. Rubin, Arul M. Chinnaiyan

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. More... »

PAGES

624-629

Journal

TITLE

Nature

ISSUE

6907

VOLUME

419

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature01075

    DOI

    http://dx.doi.org/10.1038/nature01075

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1025096861

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/12374981


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