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

2.50
Hdl Handle:
http://hdl.handle.net/10541/68740
Title:
Tumour-promoting activity of altered WWP1 expression in breast cancer and its utility as a prognostic indicator.
Authors:
Nguyen Huu, Ngoc Sa; Ryder, W David J; Zeps, N; Flasza, Marzena; Chiu, M; Hanby, A M; Poulsom, R; Clarke, Robert B; Baron, M
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.
Affiliation:
University of Manchester, Faculty of Life Sciences, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
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.
Journal:
The Journal of Pathology
Issue Date:
Sep-2008
URI:
http://hdl.handle.net/10541/68740
DOI:
10.1002/path.2385
PubMed ID:
18604872
Type:
Article
Language:
en
ISSN:
0022-3417
Appears in Collections:
All Paterson Institute for Cancer Research; Breast Biology

Full metadata record

DC FieldValue Language
dc.contributor.authorNguyen Huu, Ngoc Sa-
dc.contributor.authorRyder, W David J-
dc.contributor.authorZeps, N-
dc.contributor.authorFlasza, Marzena-
dc.contributor.authorChiu, M-
dc.contributor.authorHanby, A M-
dc.contributor.authorPoulsom, R-
dc.contributor.authorClarke, Robert B-
dc.contributor.authorBaron, M-
dc.date.accessioned2009-05-21T16:40:57Z-
dc.date.available2009-05-21T16:40:57Z-
dc.date.issued2008-09-
dc.identifier.citationTumour-promoting activity of altered WWP1 expression in breast cancer and its utility as a prognostic indicator. 2008, 216 (1):93-102 J. Pathol.en
dc.identifier.issn0022-3417-
dc.identifier.pmid18604872-
dc.identifier.doi10.1002/path.2385-
dc.identifier.urihttp://hdl.handle.net/10541/68740-
dc.description.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.en
dc.language.isoenen
dc.subjectBreast Canceren
dc.subjectTumour Markersen
dc.subjectNedd4 Familyen
dc.subjectWWP1en
dc.subject.meshAdolescent-
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAged, 80 and over-
dc.subject.meshBreast Neoplasms-
dc.subject.meshGene Expression Regulation, Neoplastic-
dc.subject.meshHumans-
dc.subject.meshMiddle Aged-
dc.subject.meshOncogenes-
dc.subject.meshPrognosis-
dc.subject.meshRegression Analysis-
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction-
dc.subject.meshTumor Markers, Biological-
dc.subject.meshUbiquitin-Protein Ligases-
dc.titleTumour-promoting activity of altered WWP1 expression in breast cancer and its utility as a prognostic indicator.en
dc.typeArticleen
dc.contributor.departmentUniversity of Manchester, Faculty of Life Sciences, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.en
dc.identifier.journalThe Journal of Pathologyen

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