The HER2 gene is over-expressed in approximately 20% of breast cancers and is the defining features of the HER2 molecular breast cancer subtypes. However, unlike with other breast cancer cell types (broadly speaking the luminal and basal types) the cell of origin of these tumours is unclear, as is the role of HER2 in the normal mammary epithelium. It is possible it has a role in stem cell function. The aims of this project are to investigate the role of HER2 in the normal mammary epithelium, the relationship between HER2 status and mammary stem/progenitor cell behaviour and the origin of HER2-positive tumours. We are using in vivo and in vitro assays to explore the effects of HER2 gain or loss-of-function in mammary epithelial cells. We are also using models of HER2-dependent breast cancer formation to determine whether HER2 cancers have high numbers of stem cells and whether the appearance and behaviour of HER2 tumours changes depending upon which cells in the stem – progenitor – differentiated cell hierarchy they are derived from.