| First Author | Del Barco Barrantes I | Year | 2018 |
| Journal | Stem Cell Reports | Volume | 10 |
| Issue | 1 | Pages | 257-271 |
| PubMed ID | 29290625 | Mgi Jnum | J:314993 |
| Mgi Id | MGI:6829390 | Doi | 10.1016/j.stemcr.2017.11.021 |
| Citation | Del Barco Barrantes I, et al. (2018) Regulation of Mammary Luminal Cell Fate and Tumorigenesis by p38alpha. Stem Cell Reports 10(1):257-271 |
| abstractText | Mammary stem and progenitor cells are essential for mammary gland homeostasis and are also candidates for cells of origin of mammary tumors. Here, we have investigated the function of the protein kinase p38alpha in the mammary gland using mice that delete this protein in the luminal epithelial cells. We show that p38alpha regulates the fate of luminal progenitor cells through modulation of the transcription factor RUNX1, an important controller of the estrogen receptor-positive cell lineage. We also provide evidence that the regulation of RUNX1 by p38alpha probably involves the kinase MSK1, which phosphorylates histone H3 at the RUNX1 promoter. Moreover, using a mouse model for breast cancer initiated by luminal cells, we show that p38alpha downregulation in mammary epithelial cells reduces tumor burden, which correlates with decreased numbers of tumor-initiating cells. Collectively, our results define a key role for p38alpha in luminal progenitor cell fate that affects mammary tumor formation. |
