Transcription Factor Activities and Gene Expression During Mouse Mammary Gland Involution

Maintenance of mammary epithelialdifferentiation and milk production during lactation isa consequence of milk removal and the presence oflactogenic hormones, particularly glucocorticoids,insulin and prolactin. After weaning the fall in lactogenichormones and milk stasis lead to involution, a processthat 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 fora new pregnancy. Each of these processes is likely todepend on the activity of specific sets of transcription factors in the mammary epithelium and stromathat ensure the timely and spatially coordinatedexpression of critical gene products such as mediatorsof apoptosis (e.g., caspase-1 and regulators of tissue remodeling events (e.g., matrixmetalloproteinases). Here we describe signaltransduction events such as activation of protein kinaseA and JNK3 and changes in the activity ofseveral transcription factors including Stat5, Stat3, NF1, Oct-1, and AP-1during the early and late phases of mammary glandinvolution. We discuss their possible role in regulatingand coordinating involution with emphasis on theapoptotic process of involution.