Minireview: hormones and mammary cell fate--what will I become when I grow up?

Abstract

Systemic hormones are key regulators of postnatal mammary gland development and play an important role in the etiology and treatment of breast cancer. Mammary ductal morphogenesis is controlled by circulating hormones, and these same hormones are also critical mediators of mammary stem cell fate decisions. Recent studies have helped further our understanding of the origin, specification, and fate of mammary stem cells during postnatal development. Here we review recent studies on the involvement of hormone receptors and several transcription factors in mammary stem/progenitor cell differentiation and lineage commitment.

Figure 1

Regulation of mammary stem cells by hormones, growth factors, and transcription factors during lineage commitment. ER-negative stem cells undergo asymmetric division to give rise to undifferentiated, ER-positive progenitor cells, which in response to estrogens, secrete paracrine factors that regulate ER-negative stem cells. These multipotent progenitor cells may also differentiate into basal-restricted (green) or luminal-restricted progenitors (dark blue), and alveolar-restricted lineages (gray) (36,37). As a result of estrogen stimulation during ductal morphogenesis, Gata-3 may specify luminal cell fate, whereas ΔN-p63 is important for basal cell lineages. During pregnancy, prolactin-mediated Gata-3 may contribute to alveolar cell development, and Elf5 establishes the secretory alveolar lineage.