title: Genetic manipulation of individual somatic mammary cells in vivo reveals a master role of STAT5a in inducing alveolar fate commitment and lactogenesis even in the absence of ovarian hormones.
abstract: Assessing the molecular control of development and cell fate in individual cells in the intact mammary epithelium has not been possible to date. By exploiting an intraductal retrovirus (RCAS)-mediated gene delivery method to introduce a marker gene, we found that ductal epithelial cells are turned over with a half time of approximately 1month in adult virgin mice. However, following RCAS-mediated introduction of a constitutively activated STAT5a (caSTAT5a), caSTAT5a-activated ductal epithelial cells expand and replace other cells in the epithelium, eventually forming a mammary gland resembling that in a late pregnant mouse, suggesting that STAT5a activation alone is sufficient to mediate pregnancy-induced mammary cell expansion, alveolar cell fate commitment, and lactogenesis. Furthermore, such caSTAT5a-induced alveolar differentiation does not require ovarian functions, although caSTAT5a-induced cell proliferation is partly reduced in ovariectomized mice. In conclusion, in this first report of studying the developmental role of a gene in a few cells in a normally developed virgin mammary ductal tree, STAT5a activation causes alveolar fate commitment and lactogenesis, and with the help of ovarian hormones, drives alveolar expansion.
authors.affiliation: Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Dong
authors.forename: Tammy
authors.initials: T
authors.lastname: Tong
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Reynado
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Rosen
authors.forename: Shixia
authors.initials: S
authors.lastname: Huang
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002645:Chickens; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010053:Ovary / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D050799:STAT5 Transcription Factor