부산대학교 도서관

The DEAD-box RNA helicases p68 (DDX5) and p72 (DDX17) have been shown to act as transcriptional coactivators 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 Keywords: p68 RNA helicase; p72 RNA helicase; oestrogen receptor-[alpha]; gene regulation; breast cancer; tamoxifen
Introduction The DEAD-box subfamily of RNA helicases, originally so named on the basis of the presence of a conserved motif having the sequence Asp-Glu-Ala-Asp, have been implicated in cellular processes [...]