Somatic loss of p53 leads to stem/progenitor cell amplification in both mammary epithelial compartments, basal and luminal

• DOI: 10.1002/stem.1429
• Publication Date: 2013-05-27T11:41:03Z
• Authors: Aurélie Chiche; Mejdi Moumen; Valérie Petit; Jos Jonkers; Daniel Medina; Marie-Ange Deugnier; Marisa M. Faraldo; Marina A. Glukhova
• Keywords: Progenitor

Mammary epithelium comprises a layer of luminal cells and basal myoepithelial cell layer. Both mammary epithelial compartments, luminal, contain stem progenitor cells, but only are capable gland regeneration upon transplantation. Aberrant expansion stem/progenitor populations is considered to contribute breast tumorigenesis. Germline deletions p53 in humans mice confer predisposition tumors, frequency abnormally high the p53-deficient mice. However, it unknown whether amplification occurs both, tissue. We used conditional gene deletion approach study role residing layers. Using two- three-dimensional culture assays, we showed that loss led clonogenic both Moreover, following deletion, acquired capacity for unlimited propagation mammosphere culture. Furthermore, limiting dilution serial transplantation assays revealed enhanced self-renewal regenerating population epithelium. Our data suggest increase activity may be, at least, partially mediated by Notch pathway. Taken together, these results strongly indicate restricts layers providing further insight into impact cancerogenesis.