Blocked acinar development, E-cadherin reduction, and intraepithelial neoplasia upon ablation of p120-catenin in the mouse salivary gland.
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.
Davis
Michael A
MA
Department of Cancer Biology, Vanderbilt University, 438 Preston Building, Nashville, Tennessee 37232, USA.
Reynolds
Albert B
AB
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics; D015820:Cadherins / Q000378:metabolism*; D002278:Carcinoma in Situ / Q000378:metabolism*; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000172:deficiency*; D002454:Cell Differentiation; D049109:Cell Proliferation; D051183:Desmoglein 1 / Q000378:metabolism; D004622:Embryo, Mammalian; D004847:Epithelial Cells / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D007150:Immunohistochemistry / Q000379:methods; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008967:Molecular Biology / Q000379:methods; D010750:Phosphoproteins / Q000172:deficiency* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012469:Salivary Glands / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism; D000095002:Delta Catenin
D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D051183:Desmoglein 1; D008562:Membrane Glycoproteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D015534:Trans-Activators; C486419:Trp63 protein, mouse; D051176:beta Catenin; D000254:Sodium-Potassium-Exchanging ATPase; D000095002:Delta Catenin; C000722349:Ctnnd1 protein, mouse