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

J Pathol. 2008 Sep;216(1):93-102. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Endosomal Sorting Complexes Required for Transport
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Middle Aged
  • Nedd4 Ubiquitin Protein Ligases
  • Oncogenes / genetics
  • Prognosis
  • Regression Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ubiquitin-Protein Ligases / genetics*
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • Biomarkers, Tumor
  • Endosomal Sorting Complexes Required for Transport
  • Nedd4 Ubiquitin Protein Ligases
  • WWP1 protein, human
  • Ubiquitin-Protein Ligases