Plasticity of mammary epithelia during normal development and neoplastic progression

Abstract

The functional unit of the mammary gland is the epithelium. It consists of luminal epithelial cells and myoepithelial cells that are generated from self-renewing stem and progenitor cells. The latter two cell types are scattered throughout the mammary epithelium and are concentrated in specialized structures, the end buds. In transplantation studies the pluripotency of mammary stem cells has been confirmed by demonstrating that they can regenerate a complete mammary gland. The ability of mammary epithelial cells to produce an elaborate ductal system during puberty and to differentiate into milk-producing alveoli during pregnancy is not only influenced by their genetic make-up, but is also governed by local molecular signals. Recent studies suggest that the transdifferentiation of epithelial cells into tumor cells is under microenvironmental control, despite the prominence of genetic mutations in breast cancer. Consequently, disturbances of tissue homeostasis can alter mammary gland development or result in preneoplastic and neoplastic pathologies. The plasticity of mammary epithelia is not limited to the entry of cells into differentiation and transdifferentiation pathways, but extends to their ability to regain facets of their preceding stage of functionality. Deciphering the molecular cues that determine cell plasticity is prerequisite for establishing a unifying concept of mammary gland development and breast tumor progression.