Our results indicate that somatic beta-catenin activating mutations contribute only to a minor part of human colorectal tumors and that germline beta-catenin mutations do not play a role in the variability of symptoms in FAP.
Some colorectal tumors with wild-type adenomatous polyposis coli gene have activating mutations in beta-catenin (encoded by CTNNB1) that result in decreased phosphorylation by GSK-3beta and increased signaling through the Tcf/Lef transcription factors.
More frequent beta-catenin gene mutations in adenomas than in aberrant crypt foci or adenocarcinomas in the large intestines of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-treated rats.
Alterations of phosphorylation sites within the CTNNB1 gene, which codes for beta-catenin has been reported to occur in about one-half of colorectal tumors without APC-gene mutations.
These results suggest that although there may be a number of mechanisms responsible for changes in beta-catenin expression in colorectal tumors, dysfunction of APC may be the major cause of this phenomenon.
TCF-4 and beta-catenin form a transcription complex, which is important for both maintenance of normal epithelium and development of colorectal tumors.
Aberrant activation of Wnt signaling caused by mutations in adenomatous polyposis coli (APC) or beta-catenin is a critical event in the development of human colorectal tumors.
Mutations in APC and beta-catenin, despite occurring in the same genetic pathway, show differing biological properties, a phenomenon that has previously been demonstrated in colorectal neoplasms.
Aberrant activation of Wnt signaling caused by mutations in the tumor suppressor adenomatous polyposis coli or beta-catenin is a critical event in the development of human colorectal tumors.
Because beta-catenin is constitutively active in the majority of colorectal tumors, it is unlikely that sFRP1 can act in the canonical Wnt response pathway.
Therefore, beta-catenin might have an impact on the capacity of colorectal tumors for invasion and metastasis, as well as dormancy, which are hallmarks of cancer.
Interestingly, the levels of Tbeta-4 mRNA, beta-catenin, c-Myc, and MMP-7 in metastatic liver lesions were relatively higher, whereas the levels of E-cadherin and Fas were significantly lower than those in the matched primary colorectal tumors.
Activator protein 2alpha associates with adenomatous polyposis coli/beta-catenin and Inhibits beta-catenin/T-cell factor transcriptional activity in colorectal cancer cells.