Activation of beta -catenin signaling in differentiated mammary secretory cells induces transdifferentiation into epidermis and squamous metaplasias.
Animal, Blotting-Western, Carcinoma-Squamous-Cell, Cell-Differentiation, Cytoplasm, Cytoskeletal-Proteins, Epidermis, Exons, Gene-Deletion, Immunohistochemistry, Metaplasia, Mice, Mice-Transgenic, Microscopy-Fluorescence, Milk-Proteins, Models-Biological, Promoter-Regions-(Genetics), Signal-Transduction, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, Time-Factors
Proc Natl Acad Sci USA 2002 Jan; 99(1):219-24.
Mammary anlagen are formed in the embryo as a derivative of the epidermis, a process that is controlled by Lef-1 and therefore possibly by beta-catenin. To investigate the role of beta-catenin signaling in mammary alveolar epithelium, we have stabilized endogenous beta-catenin in differentiating alveolar epithelium through the deletion of exon 3 (amino acids 5-80) of the beta-catenin gene. This task was accomplished in mice carrying a floxed beta-catenin gene and a Cre transgene under control of the mammary-specific whey acidic protein (WAP) gene promoter or the mouse mammary tumor virus-long terminal repeat (MMTV-LTR). Stabilized beta-catenin was obtained during the first pregnancy, and its presence resulted in the dedifferentiation of alveolar epithelium followed by a transdifferentiation into epidermal and pilar structures. Extensive squamous metaplasia, but no adenocarcinomas, developed upon beta-catenin activation during pregnancy and persisted throughout involution. These data demonstrate that the activation of beta-catenin signaling induces a program that results in loss of mammary epithelial cell differentiation and induction of epidermal structures.
Miyoshi, K; Shillingford, J M.; Le, Provost F.; Gounari, F; Bronson, R; von, Boehmer H.; Taketo, M M.; Cardiff, R D.; Hennighausen, L; and Khazaie, K, " Activation of beta -catenin signaling in differentiated mammary secretory cells induces transdifferentiation into epidermis and squamous metaplasias." (2002). Faculty Research 2000 - 2009. 342.