Tumour‐promoting activity of altered WWP1 expression in breast cancer and its utility as a prognostic indicator

Abstract WWP1 is a ubiquitin ligase, associated with the post‐translational regulation of several tumour‐promoting and tumour suppressor proteins. Here we show that WWP1 expression is up‐regulated in a subset of breast tumour cell lines and primary breast tumours. We overexpressed WWP1 in MCF10A breast epithelial cells and demonstrated increased cell growth and anchorage‐independent colony formation. RNAi knockdown of WWP1 expression in T47D and MCF7 breast tumour cell lines reduced anchorage‐independent colony formation. We used WWP1 protein expression levels, in combination with its sub‐cellular localization, to classify breast tumours into four categories. Surprisingly, a category with low/absent WWP1 expression displayed a consistently worse prognosis compared with WWP1‐expressing tumours. Importantly, the association with disease‐free survival was independent of the status of other commonly used prognostic indicators. Thus, WWP1 is a prognostic marker and may be a potential therapeutic target for a subset of breast tumours. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.