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

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, smal...

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Veröffentlicht in:Oncogene 2009-11, Vol.28 (46), p.4053-4064
Hauptverfasser: 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
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Sprache:eng
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Zusammenfassung: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
ISSN:0950-9232
1476-5594
DOI:10.1038/onc.2009.261