title: Overexpression of WWP1 is associated with the estrogen receptor and insulin-like growth factor receptor 1 in breast carcinoma.
abstract: 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 ERalpha (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.
authors.affiliation: The Center for Cell Biology and Cancer Research, Albany Medical College, Albany, NY 12208, USA. chenc@mail.amc.edu
authors.forename: Ceshi
authors.initials: C
authors.lastname: Chen
authors.forename: Zhongmei
authors.initials: Z
authors.lastname: Zhou
authors.forename: Christine E
authors.initials: CE
authors.lastname: Sheehan
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Slodkowska
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Sheehan
authors.forename: Ann
authors.initials: A
authors.lastname: Boguniewicz
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Ross
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D049109:Cell Proliferation / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D034741:RNA, Small Interfering / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D034741:RNA, Small Interfering; D013629:Tamoxifen; C471642:WWP1 protein, human; D044767:Ubiquitin-Protein Ligases; D017526:Receptor, IGF Type 1