Stress signaling and the shaping of the mammary tissue in development and cancer

Abstract

The postnatal mammary gland develops extensively through cycles of proliferation, branching, involution and remodeling. We review recent advances made in the field of stress signaling pathways and its roles in mammary gland organogenesis, how they contribute to normal organ specification and homeostasis and how its subversion by oncogenes leads to cancer. We analyze stress signaling in mammary gland biology taking into account the interrelationship with the extracellular matrix and adhesion signaling during morphogenesis. By integrating the information gathered from in vivo and three dimensional in vitro organogenesis studies, we review the novel contribution of p38(SAPK), c-Jun NH2-terminal kinase and PKR-like endoplasmic reticulum kinase (PERK) signaling pathways to the timely activation of cell death, correct establishment of polarity and growth arrest and autophagy, respectively. We also review the evidence supporting that the activation of the aforementioned stress kinases maintain breast acinar structures as part of a tumor suppressive program and that its deregulation is commonplace during breast cancer initiation.