Abstract
Studies initially focused on understanding the hormonal regulation of milk protein gene expression have evolved using transgenic and knockout mouse models to help provide new insights into the mechanisms by which hormones regulate proliferation during normal mammary gland development, and how these regulatory mechanisms have deviated in breast cancer progression. During normal mammary development, a non-uniform pattern of expression of the estrogen receptor alpha, and the progesterone and the prolactin receptors in the ductal epithelium is established. All of these receptors apparently are co-expressed in non-proliferating ductal epithelial cells. Local growth factors, which are members of the Wnt, EGF and IGF families and Rank ligand, act as mediators of systemic steroid and lactogenic hormones to stimulate proliferation of adjacent ductal epithelial cells via a paracrine mechanism. During early breast cancer progression a more uniform pattern of steroid receptor expression is observed accompanied by an apparent switch to an autocrine mechanism regulating cell proliferation.