| First Author | Bruno RD | Year | 2012 |
| Journal | Oncogene | Volume | 31 |
| Issue | 1 | Pages | 60-7 |
| PubMed ID | 21666720 | Mgi Jnum | J:179416 |
| Mgi Id | MGI:5302176 | Doi | 10.1038/onc.2011.215 |
| Citation | Bruno RD, et al. (2012) Notch-induced mammary tumorigenesis does not involve the lobule-limited epithelial progenitor. Oncogene 31(1):60-7 |
| abstractText | The mouse mammary epithelial cell hierarchy contains both multipotent stem cell as well as lineage-limited duct and lobular progenitor cell functions. The latter-also termed parity-identified mammary epithelial cells (PI-MECs)-are marked by beta-galactosidase (beta Gal) expression following pregnancy and involution in whey acidic protein promoter (WAP)-Cre/Rosa26-flox-stop-flox-lacZ (WC/R26) mice, and are the targets of tumorigenic transformation in mouse mammary tumor virus-erbB2 transgenic mice. In this study, we demonstrate that an epithelial population distinct from PI-MECs is transformed during WAP-Int3 tumorigenesis. As expected, WAP-Int3/WC/R26 triple-transgenic mice failed to undergo secretory alveolar development, failed to lactate and developed mammary tumors. Following pregnancy and involution, beta Gal+ mammary epithelial cells were found in the normal mammary tissue, but the resulting mammary tumors were all beta Gal-. WAP-Int3/WC/R26 mammary glands contained ample estrogen receptor alpha (ERalpha)+ MECs, but only rare (<1%) progesterone receptor (PR)+ and RANKL+ cells. In addition, dissociated MECs from WAP-Int3/WC/R26 glands failed to regenerate a mammary tree upon transplantation into a cleared fat-pad of a nu/nu recipient mouse. However, when mixed with normal MECs, PI-MECs from WAP-Int3/WC/R26 mice contributed progeny to the resulting functional outgrowth. The WAP-Int3/WC/R26-derived PI-MECs displayed all of the properties of fully functional lobular progenitors including giving rise to ERalpha+, PR+, smooth muscle actin+ and RANKL+ epithelial progeny. These results demonstrate that WAP-Int3 has no oncogenic effect upon PI-MECs and that the expansion of functional lobular progenitors is required for secretory alveolar development and lactation. Furthermore, lobular progenitor function is ultimately controlled by signals within its microenvironment. |
