The purpose of this study was to determine whether this D1822V [corrected] variant of the APC gene is associated with colon cancer and whether its association is influenced by other genetic or environmental factors.
The apparently low incidence of colon cancer in the African population may be ascribed either to the rare occurrence of the 'second hit' needed for polyp formation or to a lower incidence of mutations in the APC gene.
Mutations in the adenomatous polyposis coli (APC) gene, which initiate almost all human colon cancers, directly target the proto-oncogene, c-myc, by elevating beta-catenin/T-cell factor (TCF) signaling.
We have found a significant concordance between the in vitro replication errors of human DNA polymerase beta and in vivo point mutations of the adenomatous polyposis coli (APC) gene that leads to colon cancer.
A subset of cases is associated with colon cancer and APC germline mutations (Turcot syndrome), and APC and beta-catenin point mutations occur in up to 10% of sporadic cases, indicating the involvement of the Wnt pathway in the development of medulloblastoma.
To explore this idea, data from a Dutch population-based case-control study (184 cases, 259 controls) on sporadic colon cancer were used to assess associations between dietary factors and the occurrence of truncating mutations in the adenomatous polyposis coli (APC) gene in carcinomas.
Three APC isoforms that differ in their amino-terminal domains were evaluated by gene transfer experiments using a colon cancer cell line that lacks functional APC.
These results suggest that ZnCl2 inhibits the proliferation of colon cancer cells (which carry the wild-type APC gene) through stabilization of the APC protein and cell cycle arrest in the G2/M phase.
Germline mutations of APC in patients with Turcot syndrome (colon cancer and medulloblastoma), was well as somatic mutations of APC, beta-catenin, and Axin in sporadic medulloblastomas (MBs) have shown the importance of WNT signaling in the pathogenesis of MB.
It is important to evaluate the effects of proposed interventions to reduce the risk of disease among carriers of a highly penetrant mutation, such as the mutations in BRCA1 and BRCA2 for breast and ovarian cancers or in APC and MLH1 or MSH2 for colon cancer.
The purpose of this study was also to evaluate whether the LOH at the APC gene is associated with clinicopathological characteristics in sporadic colon cancer.
Promoter hypermethylation was frequently detected in more than 40% of colonic cancers and adenomas in APC, ATM, HLTF, MGMT and hMLH1 genes (p < 0.0001 vs. normal).
Mutations in APC or in beta-catenin, which are common in colon cancer, lead to constitutive activation of beta-catenin/Tcf-dependent signaling. alpha-Catenin is also found in some colon cancer cell nuclei, and loss of its expression correlates with increased beta-catenin/Tcf transcriptional activity.
We studied the effect of C(2)-ceramide and C(2)-dihydroceramide on proliferation and/or apoptosis of colon cancer cell lines in vitro and determined the role of p53 and APC proteins in these processes.
In a series of 11 microsatellite stable (MSS) and 9 microsatellite unstable (MSI) colon cancer cell lines and primary colon carcinomas (25 MSS and 28 MSI) with known ploidy stem line and APC, KRAS, and TP53 mutation status, we analyzed the promoter methylation of the following genes: hMLH1, MGMT, p16INK4a (CDKN2A alpha-transcript), p14ARF (CDKN2A beta-transcript), APC, and E-cadherin (CDH1).
Using real-time quantitative PCR, we demonstrated that several genes previously implicated in human colon cancer undergo altered expression in the APC(min) mouse adenomatous polyp, a precursor of cancer, as well as in normal-appearing surrounding mucosa.
We further showed that the colon cancer cell line expressing the wild-type APC gene was more sensitive to a DNA-methylating agent due to decreased DNA repair by long patch BER than the cell line expressing the mutant APC gene lacking the proliferating cell nuclear antigen-interacting protein-like box.