Abstract
Although Apc is well characterized as a tumor-suppressor gene in the intestine, the precise mechanism of this suppression remains to be defined. Using a novel inducible Ahcre transgenic line in conjunction with a loxP-flanked Apc allele we, show that loss of Apc acutely activates Wnt signaling through the nuclear accumulation of beta-catenin. Coincidentally, it perturbs differentiation, migration, proliferation, and apoptosis, such that Apc-deficient cells maintain a "crypt progenitor-like" phenotype. Critically, for the first time we confirm a series of Wnt target molecules in an in vivo setting and also identify a series of new candidate targets within the same setting.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adenomatous Polyposis Coli Protein / deficiency*
-
Animals
-
Cell Differentiation
-
Cell Movement
-
Cytoskeletal Proteins / metabolism
-
Immunohistochemistry
-
Intestinal Mucosa / cytology
-
Mice
-
Mice, Knockout
-
Mice, Transgenic
-
Phenotype
-
Proto-Oncogene Proteins / physiology*
-
RNA, Messenger / analysis
-
RNA, Messenger / isolation & purification
-
Signal Transduction
-
Trans-Activators / metabolism
-
Tumor Suppressor Proteins / deficiency
-
Wnt Proteins
-
beta Catenin
Substances
-
Adenomatous Polyposis Coli Protein
-
CTNNB1 protein, mouse
-
Cytoskeletal Proteins
-
Proto-Oncogene Proteins
-
RNA, Messenger
-
Trans-Activators
-
Tumor Suppressor Proteins
-
Wnt Proteins
-
beta Catenin