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FIG. 6. The transcriptional response to PRL. PRL acts on the mammary epithelium by binding to its receptor, activating a number of signaling cascades, including the Jak/Stat pathway and the mitogen-activated protein (MAP) kinase pathway. This results in the transcription of genes necessary for epithelial differentiation and formation of lobuloalveolar cells in the mammary gland. Transcript profiles of mammary glands capable of producing lobuloalveolar cells (PRLR+/+ epithelial transplants), compared to profiles of mammary glands unable to produce lobuloalveolar cells (PRLR-/- epithelial transplants), identified a number of genes within the mammary epithelium whose function is known. These genes include those important for cell structure (keratins) and components of the extracellular matrix (laminin and collagen) as well as components of junctions necessary for cell permeability (connexin-26, claudin-3 and -7). A number of transcription factors were identified that act to transcribe further genes necessary for differentiation (activator protein (AP)-2 gamma, GATA-3). These genes may include extracellular ligands such as those identified by our screen (Wnt4, amphiregulin, Rankl) that act on neighboring cells to stimulate their differentiation.
