Abstract

Mammary gland development occurs primarily in the adult. During pregnancy a new lineage, the alveolar epithelial cell, appears. These cells differentiate to produce milk during lactation and are removed in a programme of cell death coupled with tissue remodelling when lactation ceases. We are interested in two aspects of this lineage: how these cells arise from progenitors and the mechanism by which they are induced to undergo cell death.

I will discuss our recent work where we have shown that the IL-4/IL-13/Stat6 pathway is a critical regulator of alveologenesis. We have identified a novel gene that is a transcriptional target of Stat6 and is a master regulator of lineage commitment. Interestingly, ablation of this gene can rescue Gata-3 deficiency. During involution, Stat3 is essential for initiating cell death by a lysosomal-mediated pathway. Furthermore, Stat3 mediates an inflammatory and acute phase response which is associated with alternatively activated macrophages. Thus mammary epithelial cells can acquire characteristics of immune cells and this may reflect their origin.