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Blocked acinar development, E-cadherin reduction, and intraepithelial neoplasia upon ablation of p120-catenin in the mouse salivary gland.
- Source :
-
Developmental cell [Dev Cell] 2006 Jan; Vol. 10 (1), pp. 21-31. - Publication Year :
- 2006
-
Abstract
- p120 catenin is thought to be a key regulator of E-cadherin function and stability, but its role(s) in vivo is poorly understood. To examine these directly, we generated a conditional p120 knockout mouse and targeted p120 ablation to the embryonic salivary gland. Surprisingly, acinar differentiation is completely blocked, resulting in a gland composed entirely of ducts. Moreover, p120 ablation causes E-cadherin deficiency in vivo and severe defects in adhesion, cell polarity, and epithelial morphology. These changes closely phenocopy high-grade intraepithelial neoplasia, a condition that, in humans, typically progresses to invasive cancer. Tumor-like protrusions appear immediately after p120 ablation at e14 and expand into the lumen until shortly after birth, at which time the animals die with completely occluded glands. The data reveal an unexpected role for p120 in salivary acinar development and show that p120 ablation by itself induces effects consistent with a role in tumor progression.
- Subjects :
- Age Factors
Animals
Animals, Newborn
Apoptosis genetics
Catenins
Cell Differentiation
Cell Proliferation
Desmoglein 1 metabolism
Embryo, Mammalian
Gene Expression Regulation, Developmental genetics
Immunohistochemistry methods
Membrane Glycoproteins metabolism
Mice
Mice, Knockout
Molecular Biology methods
Phosphoproteins metabolism
RNA, Messenger metabolism
Reverse Transcriptase Polymerase Chain Reaction methods
Skin metabolism
Sodium-Potassium-Exchanging ATPase metabolism
Trans-Activators metabolism
beta Catenin metabolism
Delta Catenin
Cadherins metabolism
Carcinoma in Situ metabolism
Cell Adhesion Molecules deficiency
Epithelial Cells metabolism
Phosphoproteins deficiency
Salivary Glands cytology
Salivary Glands embryology
Salivary Glands metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1534-5807
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Developmental cell
- Publication Type :
- Academic Journal
- Accession number :
- 16399075
- Full Text :
- https://doi.org/10.1016/j.devcel.2005.12.004