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Overexpression of WWP1 is associated with the estrogen receptor and insulin‐like growth factor receptor 1 in breast carcinoma
Author(s) -
Chen Ceshi,
Zhou Zhongmei,
Sheehan Christine E.,
Slodkowska Elzbieta,
Sheehan Christopher B.,
Boguniewicz Ann,
Ross Jeffrey S.
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24266
Subject(s) - estrogen receptor , breast cancer , immunohistochemistry , cancer research , pathology , tamoxifen , biology , cancer , medicine
WWP1, a HECT type E3 ubiquitin ligase frequently amplified and overexpressed in breast cancer, has the potential to become a useful clinical biomarker and therapeutic target in breast cancer. Here, we performed immunohistochemical staining in formalin‐fixed and paraffin‐embedded tissue sections from 187 cases of primary invasive mammary carcinoma [137 ductal carcinomas (IDC) and 50 lobular carcinomas (ILC)] by using a monoclonal anti‐WWP1 antibody. The normal breast epithelium and adjacent benign epithelium are essentially negative for WWP1. Cytoplasmic WWP1 immunoreactivity was observed in 76/187 (40.6%) tumors and showed a positive correlation with ERα ( p = 0.05) and IGF‐1R proteins ( p = 0.001) in this cohort. The positive correlations between WWP1 and ER/IGF‐1R were also observed in a panel of 12 breast cancer cell lines by Western blot. Interestingly, the ER levels are decreased when WWP1 is silenced in ER positive MCF7 and T47D breast cancer cell lines. Finally, WWP1 ablation collectively inhibits cell proliferation with tamoxifen in MCF7 and T47D, as measured by 3 H‐thymidine incorporation assays. These findings suggest that WWP1 may play an important role in ER positive breast cancer. © 2009 UICC