Figure 5.

Parallels between normal mammary development and breast cancer progression. a Mammary gland development begins during embryogenesis resulting in a rudimentary ductal system. After onset of puberty, ductal elongation and branching morphogenesis leads to extension and arborization of the ductal tree. As the ducts extend through the mammary fat pad, differentiation of precursor cells in the TEB gives rise to the luminal and myoepithelial cells. In addition, cap cells at the leading edge of the TEB exhibit features of epithelial plasticity that are critical to the normal branching process (Inset). During pregnancy, lobuloalveolar development and side branching occur in preparation for lactation. b Breast cancer begins with the primary lesion, however as breast cancer progresses, tumor cells acquire an invasive and motile phenotype analogous to the epithelial plasticity and EMT observed in development. The epithelial plasticity and EMT permits local spread of tumor cells. Genes/pathways implicated in EMT and epithelial plasticity and misexpressed in breast cancer progression include Cripto-1, Snail/Slug/Twist, Six1, Wnt and TGF-β signaling (Inset). Local invasion of both single cell and collective migration of the tumor cells sets the stage for metastatic dissemination to distant organ sites in late stage breast cancer.