Apoptosis and remodeling of mammary gland tissue during involution proceeds through p53-independent pathways.

Mammary gland involution is a physiological process that follows lactation and results in the rapid disappearance of the entire lobulo-alveolar compartment. Coincident with the onset of involution, milk protein gene expression ceases and alveolar cells undergo programmed cell death. In mammary epithelial tissue culture cells in vitro, both p53-dependent and p53-independent apoptosis pathways have been identified. We investigated whether p53 induces apoptosis during mammary gland involution in vivo and participates in tissue remodeling. Toward this end, we examined the process of involution in the presence and absence of functional p53 in mouse models: wild-type, transgenic mice that express SV40 T-antigen specifically in mammary tissue during pregnancy; and mice that carry nonfunctional p53 alleles in their germ line. Mammary gland whole-mount and histological analyses revealed that involution and remodeling, with the concomitant disappearance of the lobulo-alveolar structures, proceeded normally in the absence of functional p53. In addition, the absence of functional p53 did not alter the involution related pattern of bax (death inducer) gene expression or the ratio of RNAs encoding bcl-xs (death inducer) to bcl-xL (survival inducer).