Regulation of mammary luminal cell differentiation and tumorigenesis by p38α. Mus musculus

Mammary stem and progenitor cells are essential for mammary gland homeostasis and are also candidates for cells of origin of mammary tumors. Here, we provide evidence that the protein kinase p38a is required for the differentiation of luminal progenitor cells through modulation of the transcription factors Runx1 and Foxa1. Moreover, using a mouse model for breast cancer initiated by luminal cells, we show that p38a downregulation in mammary epithelial cells reduces tumorigenesis, which correlates with reduced numbers of tumor-initiating cells. Our results identify p38a as a key regulator of luminal progenitor cell fate that facilitates mammary tumor formation. Overall design: Total RNA was collected from luminal population of the mammary gland purified by FACs from p38a-lox, MMTV-Cre vs MMTV-Cre and p38a-lox, MMTV-Cre, MMTV-PyMT vs MMTV-Cre, MMYV-PyMT mice. Cells were sorted on TRIzol® Plus RNA Purification Kit (Life Technologies).Total RNA was extracted using RNAeasy Micro Kit (Quiagen).