Grant: Operating Grant

Our work in the past few years has uncovered an important regulator of tumorigenesis and invasive growth of breast epithelial cells, the Met receptor. The Met receptor promotes invasive breast cancer, related to a subtype of human breast cancer, (basal like), for which there are no known therapies. Our goals in this application are to identify signals that collaborate with the Met receptor to promote breast cancer and invasion. We will use several genomic as well as biological approaches to identify and test the importance of these signals. We will develop new animal models aimed to more accurately reflect human breast cancer involving the Met receptor and a tumor suppressor gene called p53, which is often lost in human basal breast cancer. We have demonstrated that in addition to changes within the tumor, tumor progression in human breast cancer also involves changes within cells of the microenvironment of the tumor. We will develop animal models to examine how these changes are induced and develop strategies to test the importance of these tumor host cell interactions. In addition to tumor interactions with its microenvirnment, we have demonstrated that Met induced breast tumors also produce factors that promote muscle wasting (cachexia) and impact on quality of life at end stage disease and one additional goal of this proposal is to understand the molecular mechanism through which a cachexic response is promoted. Breast cancer of the basal subtype has at the moment no therapeutic targets and poor prognosis. We have established that the Met receptor can promote basal-like breast cancer and an understanding of these events at the molecular level and the generation of preclinical animal models is crucial to the design of therapeutics to target metastatic basal like breast cancer.