Fig. 5

The progesterone signaling hub in the adult mammary epithelium progesterone, upon binding to its receptor in the ER⁺/PR⁺ sensor cells (blue) activates different signaling pathways. It can stimulate cell-intrinsic proliferation by a cyclin D1-dependent mechanism (blue) and induce secreted factors like Amphiregulin, CXCL12, or Calcitonin (blue). Distinct PR⁺ cells induce WNT4, which acts on the myoepithelium where it activated canonical WNT signaling, which results in the expression of the secreted protease Adamts18 that cleaves fibronectin. As a result the ECM, part of the stem cells niche is biochemically altered with resulting activation of the hippo signaling pathway and increased transcription of FGFR signaling components (red). In other PR⁺ cells, RANKL is induced that induces the proliferation of neighboring ER⁻/PR⁻ responder cells (green) [84]. Open Access reference and author permission