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

• Published in: Oncogene Vol. 28; no. 46; pp. 4053 - 4064
• Main Authors: Wortham, N C, Ahamed, E, Nicol, S M, Thomas, R S, Periyasamy, M, Jiang, J, Ochocka, A M, Shousha, S, Huson, L, Bray, S E, Coombes, R C, Ali, S, Fuller-Pace, F V
• Format: Journal Article
• Language: English
• Published: 19.11.2009
• ISSN: 0950-9232
• DOI: 10.1038/onc.2009.261

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