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  • Oncogenomics
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E2F3 is the main target gene of the 6p22 amplicon with high specificity for human bladder cancer

Oncogene volume 25, pages 6538–6543 (2006)Cite this article

Abstract

Amplification of 6p22 occurs in about 10–20% of bladder cancers and is associated with enhanced tumour cell proliferation. Candidate target genes for the 6p22 amplicon include E2F3 and the adjacent gene NM_017774. To clarify which gene is representing the main target, we compared the prevalence of the amplification and the functional role of both genes. Amplification of E2F3 and NM_017774 was analysed by fluorescence in situ hybridization on a bladder cancer tissue microarray composed of 2317 cancer samples. Both genes showed amplification in 104 of 893 (11.6%) interpretable tumours and were exclusively found co-amplified. Additional gene expression analysis by real-time polymerase chain reaction in 12 tumour-derived cell lines revealed that amplification of 6p22 was always associated with co-overexpression of E2F3 and NM_017774. Furthermore, RNA interference was used to study the influence of reduced gene expression on cell growth. In tumour cells with and without the 6p22 amplicon, knockdown of E2F3 always lead to unequivocal reduction of proliferation, whereas knockdown of NM_017774 was only capable to slow down cell proliferation in non-amplified cells. Our findings point out that E2F3 but not NM_017774 is driving enhanced proliferation of 6p22 amplified tumour cells. We conclude that E2F3 must be responsible for the growth advantage of 6p22 amplified bladder cancer cells.

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Acknowledgements

We thank Rosmarie Chaffard, Bettina Zwyssig, Veronika Bättig, Barbara Stalder, Kirsten Struckmann and Alexander Rufle for their excellent technical support. This work was supported by the Swiss National Science Foundation (3100A0–100807/1).

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Authors and Affiliations

  1. Department of Molecular Pathology, Institute of Pathology, University of Basel, Basel, Switzerland

    M Oeggerli, C Ruiz, M Bloch & H Novotny

  2. Departement Pathology, University of Zurich, Zurich, Switzerland

    P Schraml

  3. Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    M Mirlacher, G Sauter & R Simon

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  1. M Oeggerli
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  2. P Schraml
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Correspondence to M Oeggerli or R Simon.

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Oeggerli, M., Schraml, P., Ruiz, C. et al. E2F3 is the main target gene of the 6p22 amplicon with high specificity for human bladder cancer. Oncogene 25, 6538–6543 (2006). https://doi.org/10.1038/sj.onc.1209946

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