Fig. 1.

(A) Model for NRF2 regulation in BRCA1-associated tumorigenesis. In breast tissue, estrogen induces NRF2 activation through the PI3K/AKT pathway in BRCA1-deficient cells and protects them from ROS-induced cell death. (B) Major estrogen sources in humans and mice. Red arrow indicates major tissue source of estrogen in premenopausal women. (C) Paracrine signaling in the mammary gland. In response to estrogen and progesterone, paracrine mediators promote the proliferation and differentiation of stem/progenitor cells, as well as ERα-/PR-negative luminal epithelial cells.