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- DOI: 10.1002/path.2385
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Tumour-promoting activity of altered WWP1 expression in breast cancer and its utility as a prognostic indicator
Nguyen Huu N, Ryder W, Zeps N, Flasza M, Chiu M, Hanby A, Poulsom R, Clarke RB, Baron M
Journal of Pathology. 2008;216(1):93-102.
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Full-text held externally
- DOI: 10.1002/path.2385
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.