Grant: Operating Grant

Dr. Moorehead will investigate the function of small intracellular molecules known as microRNAs (miRNAs) in breast cancer. miRNAs regulate the expression of hundreds of genes in cells including those implicated in breast cancer. miRNAs are small RNA molecules that do not produce proteins, rather they regulate the expression of other genes inside of cells. Our preliminary work has identified a number of miRNAs differentially expressed in mammary tumors compared to normal mammary tissue and between different mammary tumor subtypes. In this proposal we will examine the function of miRNAs in a subtype of mammary tumors (basal-like/claudin-low) that is typically associated with more aggressive disease and responds poorly to conventional therapies. Using our transgenic mouse model of mammary tumorigenesis and cell lines derived from these tumors, we will investigate the function of a number of miRNAs differentially expressed between normal mammary tissue and mammary tumors. These miRNAs will either be overexpressed or knocked down in mouse mammary tumor cells lines and these cell lines will be injected into the mammary fat pads of syngreneic mice to evaluate tumorigenesis in vivo. miRNAs implicated in regulating mammary tumorigenesis will be confirmed in human samples and our transgenic mouse model. It is anticipated that these studies will identify miRNAs essential for mammary tumor growth as well as produce results that will translate into novel treatment options for different types of breast cancer.