Activation of β-Catenin Signaling in Differentiated Mammary Secretory Cells Induces Transdifferentiation into Epidermis and Squamous Metaplasias
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 β-catenin signaling in mammary alveolar epithelium, we have stabilized endogenous β-catenin in differentiating alveolar epi...
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Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2002-01, Vol.99 (1), p.219-224 |
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Sprache: | eng |
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Zusammenfassung: | 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 β-catenin 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 β-catenin signaling induces a program that results in loss of mammary epithelial cell differentiation and induction of epidermal structures. |
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ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.012414099 |