Activation of beta -catenin signaling in differentiated mammary secretory cells induces transdifferentiation into epidermis and squamous metaplasias.
Document Type
Article
Publication Date
2002
Keywords
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
First Page
219
Last Page
224
JAX Source
Proc Natl Acad Sci USA 2002 Jan; 99(1):219-24.
Abstract
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.
Recommended Citation
Miyoshi K,
Shillingford JM,
Le PF,
Gounari F,
Bronson R,
von BH,
Taketo MM,
Cardiff RD,
Hennighausen L,
Khazaie K.
Activation of beta -catenin signaling in differentiated mammary secretory cells induces transdifferentiation into epidermis and squamous metaplasias. Proc Natl Acad Sci USA 2002 Jan; 99(1):219-24.