Transcription factor activities and gene expression during mouse mammary gland involution.

Maintenance of mammary epithelial differentiation and milk production during lactation is a consequence of milk removal and the presence of lactogenic hormones, particularly glucocorticoids, insulin and prolactin. After weaning the fall in lactogenic hormones and milk stasis lead to involution, a process that is mainly characterized by three events: (i) downregulation of milk protein gene expression, (ii) loss of epithelial cells by apoptosis and, (iii) tissue remodeling and preparation of the gland for a new pregnancy. Each of these processes is likely to depend on the activity of specific sets of transcription factors in the mammary epithelium and stroma that ensure the timely and spatially coordinated expression of critical gene products such as mediators of apoptosis (e.g., caspase-1 and regulators of tissue remodeling events (e.g., matrix metalloproteinases). Here we describe signal transduction events such as activation of protein kinase A and JNK and changes in the activity of several transcription factors including Stat5, Stat3, NF1, Oct-1, and AP-1 during the early and late phases of mammary gland involution. We discuss their possible role in regulating and coordinating involution with emphasis on the apoptotic process of involution.