Activation of β-catenin signaling in differentiated mammary secretory cells induces transdifferentiation into epidermis and squamous metaplasias

Keiko Miyoshi, Jonathan M. Shillingford, Fabienne Le Provost, Fotini Gounari, Roderick Bronson, Harald Von Boehmer, Makoto M. Taketo, Robert Cardiff, Lothar Hennighausen, Khashayarsha Khazaie

Research output: Contribution to journalArticle

101 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)219-224
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number1
DOIs
StatePublished - Jan 8 2002

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Cell Transdifferentiation
Catenins
Metaplasia
Epidermis
Breast
Epithelium
Genes
Mouse mammary tumor virus
Pregnancy
Terminal Repeat Sequences
Transgenes
Hair
Cell Differentiation
Exons
Adenocarcinoma
Embryonic Structures
Epithelial Cells
Amino Acids

Keywords

  • Cell identity
  • Cre
  • Dedifferentiation
  • Mammary gland
  • Wnt-signaling

ASJC Scopus subject areas

  • General

Cite this

Activation of β-catenin signaling in differentiated mammary secretory cells induces transdifferentiation into epidermis and squamous metaplasias. / Miyoshi, Keiko; Shillingford, Jonathan M.; Le Provost, Fabienne; Gounari, Fotini; Bronson, Roderick; Von Boehmer, Harald; Taketo, Makoto M.; Cardiff, Robert; Hennighausen, Lothar; Khazaie, Khashayarsha.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 1, 08.01.2002, p. 219-224.

Research output: Contribution to journalArticle

Miyoshi, Keiko ; Shillingford, Jonathan M. ; Le Provost, Fabienne ; Gounari, Fotini ; Bronson, Roderick ; Von Boehmer, Harald ; Taketo, Makoto M. ; Cardiff, Robert ; Hennighausen, Lothar ; Khazaie, Khashayarsha. / Activation of β-catenin signaling in differentiated mammary secretory cells induces transdifferentiation into epidermis and squamous metaplasias. In: Proceedings of the National Academy of Sciences of the United States of America. 2002 ; Vol. 99, No. 1. pp. 219-224.
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