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The DEAD-box protein p72 regulates ERα-/oestrogen-dependent transcription and cell growth, and is associated with improved survival in ERα-positive breast cancer

Oncogene volume 28, pages 4053–4064 (2009)Cite this article

Abstract

The DEAD-box RNA helicases p68 (DDX5) and p72 (DDX17) have been shown to act as transcriptional co-activators for a diverse range of transcription factors, including oestrogen receptor-α (ERα). Here, we show that, although both proteins interact with and co-activate ERα in reporter gene assays, small interfering RNA-mediated knockdown of p72, but not p68, results in a significant inhibition of oestrogen-dependent transcription of endogenous ERα-responsive genes and oestrogen-dependent growth of MCF-7 and ZR75-1 breast cancer cells. Furthermore, immunohistochemical staining of ERα-positive primary breast cancers for p68 and p72 indicate that p72 expression is associated with an increased period of relapse-free and overall survival (P=0.006 and 0.016, respectively), as well as being inversely associated with Her2 expression (P=0.008). Conversely, p68 shows no association with relapse-free period, or overall survival, but it is associated with an increased expression of Her2 (P=0.001), AIB-1 (P<0.001) and higher tumour grade (P=0.044). Our data thus highlight a crucial role for p72 in ERα co-activation and oestrogen-dependent cell growth and provide evidence in support of distinct but important roles for both p68 and p72 in regulating ERα activity in breast cancer.

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Acknowledgements

This work was supported by grants from the Breast Cancer Campaign, Association for International Cancer Research, Cancer Research UK and the Breast Cancer Research Trust. We are grateful for support from the NIHR Biomedical Research Centre funding scheme, and thank David Meek, Malcolm Parker and lab members for helpful discussions.

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Author notes

  1. N C Wortham and E Ahamed: These authors contributed equally to this work.

Authors and Affiliations

  1. Centre for Oncology and Molecular Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK

    N C Wortham, S M Nicol & F V Fuller-Pace

  2. Department of Oncology, Imperial College London, Hammersmith Hospital Campus, London, UK

    E Ahamed, R S Thomas, M Periyasamy, J Jiang, A M Ochocka, R C Coombes & S Ali

  3. Department of Histopathology, Imperial College London, Charing Cross Hospital, London, UK

    J Jiang & S Shousha

  4. Statistical Advisory Service, Imperial College London, South Kensington Campus, London, UK

    L Huson

  5. Tayside Tissue Bank, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK

    S E Bray

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Correspondence to S Ali or F V Fuller-Pace.

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

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Wortham, N., Ahamed, E., Nicol, S. et al. The DEAD-box protein p72 regulates ERα-/oestrogen-dependent transcription and cell growth, and is associated with improved survival in ERα-positive breast cancer. Oncogene 28, 4053–4064 (2009). https://doi.org/10.1038/onc.2009.261

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