Intestinal dysplasia and adenoma in transgenic mice after overexpression of an activated beta-catenin.
Mutations in the adenomatous polyposis coli gene or activating mutations in the beta-catenin gene itself are thought to be responsible for the excessive beta-catenin signaling involved in intestinal carcinogenesis. We generated transgenic mice that expressed large amounts of a NH2-terminally truncated mutant beta-catenin (deltaN131beta-catenin) in the intestine. These mice had multifocal dysplastic lesions in the small intestine, reminiscent of the early lesions observed in the mouse models of familial adenomatous polyposis. The number of apoptotic cells in the villi of these transgenic mice was 3-4-fold higher than in nontransgenic mice. Expression of the truncated beta-catenin mutant in the kidney led to the development of severe polycystic kidney disease. Our findings support the concept that deregulation of the beta-catenin signaling pathway is the major oncogenic consequence of adenomatous polyposis coli mutations in intestinal neoplasia.
Romagnolo
B
B
Institut National de la Santé et de la Recherche Médicale U129, ICGM, Paris, France.
Berrebi
D
D
Saadi-Keddoucci
S
S
Porteu
A
A
Pichard
A L
AL
Peuchmaur
M
M
Vandewalle
A
A
Kahn
A
A
Perret
C
C
D000236:Adenoma / Q000235:genetics*; D011125:Adenomatous Polyposis Coli / Q000235:genetics; D000818:Animals; D015820:Cadherins / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D007410:Intestinal Diseases / Q000235:genetics; D007414:Intestinal Neoplasms / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D015534:Trans-Activators; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D015820:Cadherins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin