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Polycomb-group oncogenes EZH2, BMI1, and RING1 are overexpressed in prostate cancer with adverse pathologic and clinical features.

Authors: Van Leenders, GJ  Dukers, D  Hessels, D  Van den Kieboom, SW  Hulsbergen, CA  Witjes, JA  Otte, AP  Meijer, CJ  Raaphorst, FM 
Citation: van Leenders GJ, etal., Eur Urol. 2007 Aug;52(2):455-63. Epub 2006 Nov 17.
Pubmed: (View Article at PubMed) PMID:17134822
DOI: Full-text: DOI:10.1016/j.eururo.2006.11.020

OBJECTIVES: Polycomb group (PcG) proteins are involved in maintenance of cell identity and proliferation. The protein EZH2 is overexpressed in disseminated prostate cancer, implicating a role of PcG complexes in tumor progression. In this study, we evaluated the expression of eight members of both PcG complexes in clinicopathologically defined prostate cancer. METHODS: Components of both PcG protein complexes PRC2 (EZH2, EED, YY1) and PRC1 (BMI1, RING1, HPH1, HPC1, HPC2) were immunohistochemically identified in tissue microarrays of 114 prostate cancer patients. Protein expression was semi-quantitatively scored and correlated with pathologic parameters and recurrence of prostate-specific antigen (PSA). RESULTS: Whereas BMI1, RING1, HPC1 and HPH1 were all abundantly present in normal and malignant prostate epithelium, expression of EZH2 occurred in only <10% of cells. Expression of EZH2, BMI1 and RING1 were all significantly enhanced in tumours with Gleason score (GS) > or = 8, extraprostatic extension, positive surgical margins, and PSA recurrence. When only the subgroup of GS < or = 6 was considered, representing the tumour grade in the majority of needle biopsies, EZH2 and BMI1 were also predictive for PSA recurrence. In a multivariable analysis, BMI1 was the only PcG protein with an independent prognostic value. CONCLUSIONS: PcG proteins EZH2, BMI1, and RING1 are associated with adverse pathologic features and clinical PSA recurrence of prostate cancer. Whereas BMI1 and RING1 are abundantly present in prostate cancer, EZH2 is expressed at relatively low levels, making it a less obvious target for therapy.


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CRRD Object Information
CRRD ID: 10755355
Created: 2016-01-26
Species: All species
Last Modified: 2016-01-26
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.