Tumour-promoting activity of altered WWP1 expression in breast cancer and its utility as a prognostic indicator.
AuthorsNguyen Huu, Ngoc Sa
Ryder, W David J
Hanby, A M
Clarke, Robert B
AffiliationUniversity of Manchester, Faculty of Life Sciences, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
MetadataShow full item record
AbstractWWP1 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.
CitationTumour-promoting activity of altered WWP1 expression in breast cancer and its utility as a prognostic indicator. 2008, 216 (1):93-102 J. Pathol.
JournalThe Journal of Pathology
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