Investigating the role of Wnt signalling in lobuloalveolar development of the mammary gland

The Wnt signalling pathway regulates postnatal lobuloalveolar development. Expression of Wnt inhibitors blocks lobuloalveolar development, whereas expression of Wnt pathway activators induces precocious lobular development. Wnt ligands have been suggested to operate by regulating the proliferation and differentiation of lobuloalveolar progenitor cells during pregnancy. However, the lobular developmental switch is difficult to study using current experimental systems due to a mammary-specific 'Catch 22' in which promoters such as MMTV and WAP are only expressed after commitment to the lobular lineage. We are therefore developing an inducible transgene expression system which expresses Wnt regulators in all mammary epithelial cell types prior to and during lobuloalveolar development. In addition we are using Wnt-reporters to identify Wnt-responsive cells during these early developmental stages and aim to use stem cell markers to further characterise this subset of cells. Many studies support the idea that breast cancer results from oncogenic changes to mammary stem cells. This work should help establish the role Wnt signalling plays in the expansion of lobular progenitor cells and investigate the effect that switching the Wnt pathway on or off has on lobuloalveolar development.