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

N.S. Nguyen Huu, W.D. Ryder, Nikolajs Zeps, M. Flasza, M. Chiu, A.M. Hanby, R. Poulsom, R.B. Clarke, M. Baron

    Research output: Contribution to journalArticlepeer-review

    24 Citations (Scopus)

    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 subcellular 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 (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
    Original languageEnglish
    Pages (from-to)93-102
    JournalJournal of Pathology
    Volume216
    Issue number1
    DOIs
    Publication statusPublished - 2008

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