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

N. C. Wortham, E. Ahamed, S.M. Nicol, R. S. Thomas, M. Periyasamy, J. Jiang, A. M. Ochocka, S. Shousha, L. Huson, S. E. Bray, R. C. Coombes, S. Ali (Lead / Corresponding author), F.V. Fuller-Pace (Lead / Corresponding author)

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    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-alpha (ER alpha). Here, we show that, although both proteins interact with and co-activate ER alpha 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 ER alpha-responsive genes and oestrogen-dependent growth of MCF-7 and ZR75-1 breast cancer cells. Furthermore, immunohistochemical staining of ER alpha-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 ER alpha co-activation and oestrogen-dependent cell growth and provide evidence in support of distinct but important roles for both p68 and p72 in regulating ER alpha activity in breast cancer. Oncogene (2009) 28, 4053-4064; doi:10.1038/onc.2009.261; published online 31 August 2009

    Original languageEnglish
    Pages (from-to)4053-4064
    Number of pages12
    JournalOncogene
    Volume28
    Issue number46
    DOIs
    Publication statusPublished - 19 Nov 2009

    Keywords

    • p68 RNA helicase
    • p72 RNA helicase
    • oestrogen receptor-alpha
    • gene regulation
    • breast cancer
    • tamoxifen
    • ESTROGEN-RECEPTOR-ALPHA
    • P68 RNA HELICASE
    • PHOSPHORYLATION
    • COACTIVATOR
    • ACTIVATION
    • TAMOXIFEN
    • PROMOTER
    • COMPLEX
    • DIFFERENTIATION
    • IDENTIFICATION

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