ABSTRACT
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 (ß 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, ß Gal+ mammary epithelial cells were found in the normal mammary tissue, but the resulting mammary tumors were all ß Gal-. WAP-Int3/WC/R26 mammary glands contained ample estrogen receptor alpha (ERα)+ 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 ERα+, 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.
Subject(s)
Epithelial Cells/physiology , Mammary Neoplasms, Experimental/etiology , Proto-Oncogene Proteins/physiology , Receptors, Notch/physiology , Stem Cells/physiology , Animals , Female , Male , Mice , Milk Proteins/metabolism , Receptor, Notch4Subject(s)
Combat Disorders/psychology , MMPI , Stress Disorders, Post-Traumatic/psychology , Veterans/psychology , Humans , Male , Psychometrics , VietnamABSTRACT
An unusual case of hydranencephaly was reported. The child survived for 19 years and showed evidence on three occasions of an increase in eyeblink rate with tactile reinforcement. Diagnosis was confirmed by an autopsy which revealed no preserved cortex in either hemisphere.
