TY - JOUR
T1 - Activation of β-catenin signaling in differentiated mammary secretory cells induces transdifferentiation into epidermis and squamous metaplasias
AU - Miyoshi, Keiko
AU - Shillingford, Jonathan M.
AU - Le Provost, Fabienne
AU - Gounari, Fotini
AU - Bronson, Roderick
AU - Von Boehmer, Harald
AU - Taketo, Makoto M.
AU - Cardiff, Robert D.
AU - Hennighausen, Lothar
AU - Khazaie, Khashayarsha
PY - 2002/1/8
Y1 - 2002/1/8
N2 - 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 β-catenin. To investigate the role of βcatenin signaling in mammary alveolar epithelium, we have stabilized endogenous β-catenin in differentiating alveolar epithelium through the deletion of exon 3 (amino acids 5-80) of the β-catenin gene. This task was accomplished in mice carrying a floxed β-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 β-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 β-catenin activation during pregnancy and persisted throughout involution. These data demonstrate that the activation of βcatenin signaling induces a program that results in loss of mammary epithelial cell differentiation and induction of epidermal structures.
AB - 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 β-catenin. To investigate the role of βcatenin signaling in mammary alveolar epithelium, we have stabilized endogenous β-catenin in differentiating alveolar epithelium through the deletion of exon 3 (amino acids 5-80) of the β-catenin gene. This task was accomplished in mice carrying a floxed β-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 β-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 β-catenin activation during pregnancy and persisted throughout involution. These data demonstrate that the activation of βcatenin signaling induces a program that results in loss of mammary epithelial cell differentiation and induction of epidermal structures.
KW - Cell identity
KW - Cre
KW - Dedifferentiation
KW - Mammary gland
KW - Wnt-signaling
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U2 - 10.1073/pnas.012414099
DO - 10.1073/pnas.012414099
M3 - Article
C2 - 11773619
AN - SCOPUS:0037039355
SN - 0027-8424
VL - 99
SP - 219
EP - 224
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 1
ER -