Grant: Operating Grant - Priority Announcement: Breast Cancer

PTEN is a critical tumour suppressor that prevents breast cancer formation. Clinical observations have shown that a loss of PTEN occurs in high percentages (up to 50%) of HER2-positive and basal-like breast cancers, the two subgroups that are associated with a poor outcome. However, our knowledge on how PTEN is inactivated in breast cancer is incomplete. We propose here that although a large proportion of breast cancers contain PTEN, the protein may not function properly. Consistent with our hypothesis, we identified a protein (called SIPL1) that reduces PTEN function. Furthermore, we demonstrated that SIPL1 inactivates PTEN in breast cancer cells and importantly, associates with a loss of PTEN function in primary breast cancers obtained directly from patients. This strongly suggests that SIPL1 inactivates PTEN during breast cancer formation. In this study, we will closely examine the relationship between SIPL1 and the loss of PTEN function in breast cancer as well as how SIPL1 reduces PTEN function during breast cancer formation. As the loss of PTEN function is a major cause of therapeutic failure for breast cancer, this research may lead to the development of novel diagnostic and therapeutic approaches for patients with breast cancer.