p63 is a prosurvival factor in the adult mammary gland during post-lactational involution, affecting PI-MECs and ErbB2 tumorigenesis

摘要: In embryogenesis, p63 is essential to develop mammary glands. the adult gland, highly expressed in basal cell layer that comprises myoepithelial and interspersed stem/progenitor cells, has limited expression luminal epithelial cells. skin, a crucial role maintenance of stem However, it unclear whether also an equivalent as factor epithelium. We show vivo for survival parity-identified cells (PI-MECs), pregnancy-induced heterogeneous population survives post-lactational involution contain multipotent progenitors give rise alveoli ducts subsequent pregnancies. p63+/− glands are normal virgin, pregnant lactating states. Importantly, however, during apoptotic phase threefold increase death, concomitant with increased activation oncostatin M/Stat3 p53 pro-apoptotic pathways, which responsible this phase. Thus, physiologic antagonist these pathways specifically regressive stage. After restructuring when complete, mice again exhibit architecture by conventional histology. using RosaLSL-LacZ;WAP-Cre transgenics (LSL-LacZ, lox-stop-lox β-galactosidase), genetic labeling system PI-MECs, we find have 30% reduction number PI-MEC their derivatives. PI-MECs cellular targets pregnancy-promoted ErbB2 tumorigenesis. Consistent pool reduction, one-time partially protected from breast tumorigenesis, exhibiting extended tumor-free overall survival, reduced tumor multiplicity compared p63+/+ littermates. Conversely, virgin heterozygosity provides no advantage. sum, our data establish important pregnancy-identified tissue vivo.