EDD E3 Ligase in Survival and Drug Resistance of Breast Cancer Cells

Breast cancer (BCa) is the most common malignancy in Canadian women, killing 1 in 30 of 24,000 women diagnosed with it in 2014. Although male breast cancer accounts for 1% of all BCa, 60 of 210 diagnosed men died last year. These statistics are an impetus for a better understanding of the pathology of BCa and finding new therapies for early diagnosis, prevention, and treatment. Regardless of gender, normal and malignant breast cells have receptors for steroid hormones estrogen and progesterone, and for epidermal growth factor. Though less recognized, normal and malignant breast cells also have a receptor for protein hormone prolactin. All these hormones/growth factor stimulate BCa cell growth. We have reported that estrogen, progesterone and prolactin increase levels of an enzyme called EDD in BCa cells. EDD levels are known to be increased in BCa and ovarian cancers, implying a role in cancer growth. Recent reports show that EDD increases survival and drug resistance of ovarian cancer cells, whereas loss of EDD arrests growth of bone cancer cells. We propose to determine the role of EDD in regulating growth, survival rates, and drug resistance of BCa cells. We will manipulate the EDD levels in BCa cells in culture, and determine the effects of EDD depletion or EDD abundance on cell growth, survival, and resistance to chemotherapeutic drugs used in BCa treatment. A better understanding of the way EDD acts is essential for designing strategies to counteract its action in BCa. To investigate the role EDD E3 ligase in the activation of prosurvival pathways to promote viability and/or drug resistance in breast cancer cells.EDD levels will be altered in breast cancer cells using siRNAs or an expression vector. The effects of EDD depletion or EDD overexpression on cell viability, apoptosis, cell cycle progression, expression of prosurvival genes, and resistance to chemotherapeutic drugs will be determined.