Cell death during mammary involution

Pregnancy and lactation induce dramatic changes to the function and morphology of the mammary gland, including proliferation of breast epithelial cells, elaboration of secretory ducts and alveoli, and onset of milk production. Once nursing ceases, all of these changes are reversed, returning the tissue to a condition much like its pre-pregnant state. In the involuting mammary of the mouse, the death of differentiated epithelial cells occurs in at least 2 defined stages: an initial wave of apoptic cell death that peaks 2 days after weaning, and a later stage, beginning a few days later, when the extracellular matrix surrounding the mammary alveoli begins to break down. Song and colleagues report here that the first wave of apoptosis requires the binding of the cell death regulatory protein Fas to its ligand FasL. By following the expression of Fas and FasL, the authors show that, although the two proteins are each present at different times before during and after pregnancy, they are not co-expressed at substantial levels until the early phase of involution. Furthermore, in mutant animals lacking one or the other of these gene products, epithelial cell death is delayed by several days. Song et al. conclude that the initial phase of apoptosis is lacking in these animals, consistent with reports that other players in the Fas-dependent cell death pathway are active during the early phase of involution. More work in this system will be required to learn how the Fas-independent cell death seen in the mutant animals relates to the normal second phase of involution.