Mammary stem cells and their regulation by steroid hormones

Sustained exposure to estrogen and progesterone is a well-established risk factor for breast cancer. These hormones play a central role in the female reproductive cycle, in which they control morphogenesis of the mammary gland during puberty, ovulatory cycles and pregnancy. Mouse mammary stem cells (MaSCs) have recently been discovered to be highly responsive to female hormones, despite lacking expression of the estrogen and progesterone receptors. The inhibition of MaSCs by hormone receptor antagonists further suggests that these cells contribute to oncogenesis. Identification of paracrine mediators of hormone signaling to MaSCs may lead to the development of novel inhibitors that drive MaSCs into a more quiescent state. In this context, inhibition of the receptor activator of NF-κB/receptor activator of NF-κB ligand signaling pathway has profound implications for the prevention of breast cancer.