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

Oncogene. 2009 Nov 19;28(46):4053-64. doi: 10.1038/onc.2009.261. Epub 2009 Aug 31.


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 (ERalpha). Here, we show that, although both proteins interact with and co-activate ERalpha 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 ERalpha-responsive genes and oestrogen-dependent growth of MCF-7 and ZR75-1 breast cancer cells. Furthermore, immunohistochemical staining of ERalpha-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 ERalpha co-activation and oestrogen-dependent cell growth and provide evidence in support of distinct but important roles for both p68 and p72 in regulating ERalpha activity in breast cancer.

MeSH terms

  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • COS Cells
  • Cell Proliferation* / drug effects
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Chlorocebus aethiops
  • DEAD-box RNA Helicases / metabolism
  • DEAD-box RNA Helicases / physiology*
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism
  • Estrogen Receptor alpha / physiology*
  • Estrogens / metabolism
  • Estrogens / pharmacology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Nuclear Receptor Coactivator 1 / metabolism
  • Nuclear Receptor Coactivator 1 / physiology
  • Protein Binding
  • Transcription, Genetic* / drug effects
  • Transcription, Genetic* / genetics
  • Transcriptional Activation
  • Tumor Cells, Cultured


  • Estrogen Receptor alpha
  • Estrogens
  • NCOA1 protein, human
  • Nuclear Receptor Coactivator 1
  • DDX17 protein, human
  • DEAD-box RNA Helicases