Tumour-promoting activity of altered WWP1 expression in breast cancer and its utility as a prognostic indicator.
Nguyen Huu, Ngoc Sa ; Ryder, W David J ; Zeps, N ; Flasza, Marzena ; Chiu, M ; Hanby, A M ; Poulsom, R ; Clarke, Robert B ; Baron, M
Nguyen Huu, Ngoc Sa
Ryder, W David J
Zeps, N
Flasza, Marzena
Chiu, M
Hanby, A M
Poulsom, R
Clarke, Robert B
Baron, M
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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.
Description
Date
2008-09
Publisher
Keywords
Breast Cancer
Tumour Markers
Nedd4 Family
WWP1
Tumour Markers
Nedd4 Family
WWP1
Type
Article
Citation
Tumour-promoting activity of altered WWP1 expression in breast cancer and its utility as a prognostic indicator. 2008, 216 (1):93-102 J. Pathol.