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

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 estrogen receptor α (ERα). Here, we show that, although both proteins interact with and co-activate ERα in reporter gene assays, siRNA-mediated knockdown of p72, but not p68, results in a significant inhibition of estrogen-dependent transcription of endogenous ERα-responsive genes and estrogen-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 p=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 estrogen-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.