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Contribution of the WW domain-containing oxidoreductase, WWOX, gene toward mammary tumorigenesis

Final Report Summary - WOX IN BREAST CANCER (Contribution of the WW domain-containing oxidoreductase, WWOX, gene toward mammary tumorigenesis)

WWOX in breast carcinogenesis.

The WWOX gene encodes a 46kDa tumor suppressor spanning a genomic region that is frequently altered in breast cancer. Homozygous and hemizygous deletions were reported in several types of cancer including breast cancer. Numerous studies have shown that overexpression of WWOX in breast cancer cells renders them more sensitive to apoptosis and resistant to tumor formation in nude mice. Monitoring of Wwox-heterozygous mice in partially pure C3H background mice revealed increased incidence of mammary tumor formation as compared to control wild type littermates (1). These results and others promoted us to address the specific contribution of WWOX to mammary tumorigenesis. We took advantage of mouse models and generated a conditional-knockout mouse to ablate the Wwox gene specifically in mammary gland epithelium. Successful generation and validation of the mouse model was completed. Using this model, we aim to examine the consequences of WWOX deletion on mammary gland development and tumorigenesis. We also performed a proteomic experiment to identify WWOX partners that explain WWOX tumor suppressor activity in breast cancer cells. Our analysis revealed novel hits that help understanding the complex contribution of WWOX toward several phenotypes in homeostasis and in cancer (2).
1. Abdeen S, Salah Z, Mally B, Smith Y, Tufail, R, Abu-Odeh M, Zanesi N, Croce CM, Nawaz Z, Aqeilan RI. Wwox inactivation enhances mammary tumorigenesis. Oncogene. 2011; 30(36):3900-6.
2. Del Mare S, Salah Z, Aqeilan RI: Wwox: Its genomics, partners, and functions. J Cell Biochem 2009;108:737-745.