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Transcription factor E2F3 overexpressed in prostate cancer independently predicts clinical outcome

Oncogene volume 23, pages 5871–5879 (2004)Cite this article

Abstract

E2F transcription factors, including E2F3, directly modulate expression of EZH2. Recently, overexpression of the EZH2 gene has been implicated in the development of human prostate cancer. In tissue microrarray studies we now show that expression of high levels of nuclear E2F3 occurs in a high proportion (98/147, 67%) of human prostate cancers, but is a rare event in non-neoplastic prostatic epithelium suggesting a role for E2F3 overexpression in prostate carcinogenesis. Patients with prostate cancer exhibiting immunohistochemically detectable nuclear E2F3 expression have poorer overall survival (P=0.0022) and cause-specific survival (P=0.0047) than patients without detectable E2F3 expression. When patients are stratified according to the maximum percentage of E2F3-positive nuclei identified within their prostate cancers (up to 20, 21–40%, etc.), there is an increasingly significant association between E2F3 staining and risk of death both for overall survival (P=0.0014) and for cause-specific survival (P=0.0004). Multivariate analyses select E2F3 expression as an independent factor predicting overall survival (unstratified P=0.0103, stratified P=0.0086) and cause-specific survival (unstratified P=0.0288, stratified P=0.0072). When these results are considered together with published data on EZH2 and on the E2F3 control protein pRB, we conclude that the pRB–E2F3–EZH2 control axis may have a critical role in modulating aggressiveness of individual human prostate cancer.

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Acknowledgements

This work is supported by the National Cancer Research Institute, the Cancer Research UK, the Medical Research Council and TR Golden Charitable Trust. We thank Christine Bell for typing this manuscript. Alison Falconer is supported by a grant from the Community Fund through the AICR.

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Authors and Affiliations

  1. Department of Pathology and Molecular Genetics, University of Liverpool, Duncan Building, Liverpool, UK

    Christopher S Foster & Andrew R Dodson

  2. Section of Cancer Genetics, Male Urological Cancer Research Centre, Institute of Cancer Research, Sutton, Surrey, UK

    Alison Falconer, Christine Southgate & Rosalind Eeles

  3. Section of Molecular Carcinogenesis, Male Urological Cancer Research Centre, Institute of Cancer Research, Sutton, Surrey, UK

    Nening Dennis, Anne Fletcher, Sameer Jhavar, Andrew Feber & Colin S Cooper

  4. The Royal Marsden NHS Trust, Sutton, UK

    Andrew R Norman, Anna Dowe & David Dearnaley

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Correspondence to Colin S Cooper.

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Foster, C., Falconer, A., Dodson, A. et al. Transcription factor E2F3 overexpressed in prostate cancer independently predicts clinical outcome. Oncogene 23, 5871–5879 (2004). https://doi.org/10.1038/sj.onc.1207800

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