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TMPRSS2-ERG fusion, a common genomic alteration in prostate cancer activates C-MYC and abrogates prostate epithelial differentiation

Oncogene volume 27, pages 5348–5353 (2008)Cite this article

Abstract

The high prevalence of TMPRSS2-ERG rearrangements (∼60%) in prostate cancer (CaP) leads to androgenic induction of the ETS-related gene (ERG) expression. However, the biological functions of ERG overexpression in CaP remain to be understood. ERG knockdown in TMPRSS2-ERG expressing CaP cells induced striking morphological changes and inhibited cell growth both in cell culture and SCID mice. Evaluation of the transcriptome and specific gene promoters in ERG siRNA-treated cells and investigation of gene expression signatures of human prostate tumors revealed ERG-mediated activation of C-MYC oncogene and the repression of prostate epithelial differentiation genes (PSA and SLC45A3/Prostein). Taken together, these data combining cell culture and animal models and human prostate tumors reveal that ERG overexpression in prostate tumor cells may contribute to the neoplastic process by activating C-MYC and by abrogating prostate epithelial differentiation as indicated by prostate epithelial specific markers.

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Acknowledgements

Authors express sincere thanks to Ms Lakshmi Ravindranath, Ms Atekelt Y Tadese, Ms Suma Ravulapalli and Mr Christopher Cook for their superb technical support of this study. The prostate tissue specimens used in this study were obtained under an IRB-approved protocol at Walter Reed Army Medical Center. This work was funded by the CPDR through an ongoing grant from the US Army Medical Research and Materiel Command, NIH Grants RO1 DK065977 to S.S and G.P. and RO1 CA106653 to S.S. and A.D. The views expressed in this manuscript are those of the authors and do not reflect the official policy of the Department of the Army, Department of Defense or the US Government.

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Author notes

  1. C Sun and A Dobi: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Rockville, MD, USA

    C Sun, A Dobi, A Mohamed, H Li, R L Thangapazham, B Furusato, S Shaheduzzaman, S-H Tan, G Vaidyanathan, E Whitman, D J Hawksworth, Y Chen, T Sreenath, G Petrovics, D G McLeod & S Srivastava

  2. Department of Genitourinary Pathology, Armed Forces Institute of Pathology, Washington, DC, USA

    B Furusato & I A Sesterhenn

  3. Department of Surgery, Urology Service, Walter Reed Army Medical Center, Washington, DC, USA

    E Whitman, D J Hawksworth & D G McLeod

  4. Division of Retrovirology, Walter Reed Army Institute of Research, Rockville, MD, USA

    M Nau & M Vahey

  5. Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA

    V Patel & J S Gutkind

  6. US Military Cancer Institute, Washington, DC, USA

    A Dobi, I A Sesterhenn, D G McLeod & S Srivastava

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  1. C Sun
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Corresponding authors

Correspondence to A Dobi or S Srivastava.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Sun, C., Dobi, A., Mohamed, A. et al. TMPRSS2-ERG fusion, a common genomic alteration in prostate cancer activates C-MYC and abrogates prostate epithelial differentiation. Oncogene 27, 5348–5353 (2008). https://doi.org/10.1038/onc.2008.183

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