| First Author | Cagnet S | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 4723 |
| PubMed ID | 30413705 | Mgi Jnum | J:268522 |
| Mgi Id | MGI:6268103 | Doi | 10.1038/s41467-018-07175-0 |
| Citation | Cagnet S, et al. (2018) Oestrogen receptor alpha AF-1 and AF-2 domains have cell population-specific functions in the mammary epithelium. Nat Commun 9(1):4723 |
| abstractText | Oestrogen receptor alpha (ERalpha) is a transcription factor with ligand-independent and ligand-dependent activation functions (AF)-1 and -2. Oestrogens control postnatal mammary gland development acting on a subset of mammary epithelial cells (MECs), termed sensor cells, which are ERalpha-positive by immunohistochemistry (IHC) and secrete paracrine factors, which stimulate ERalpha-negative responder cells. Here we show that deletion of AF-1 or AF-2 blocks pubertal ductal growth and subsequent development because both are required for expression of essential paracrine mediators. Thirty percent of the luminal cells are ERalpha-negative by IHC but express Esr1 transcripts. This low level ERalpha expression through AF-2 is essential for cell expansion during puberty and growth-inhibitory during pregnancy. Cell-intrinsic ERalpha is not required for cell proliferation nor for secretory differentiation but controls transcript levels of cell motility and cell adhesion genes and a stem cell and epithelial mesenchymal transition (EMT) signature identifying ERalpha as a key regulator of mammary epithelial cell plasticity. |
