Ethanol-induced mast cell-mediated inflammation leads to increased susceptibility of intestinal tumorigenesis in the APC Δ468 min mouse model of colon cancer.
This report is the first description of how a second hit to the APC gene can be involved in carcinogenesis of the jejunum in familial adenomatous polyposis.
The relative contribution that telomere dysfunction and/or APC mutation play in the chromosome instability that occurs during colorectal tumorigenesis is not clear.
In this study, we examined the role of hERG1 in colorectal carcinogenesis using two mouse models: adenomatous polyposis coli (Apc(min/+) ) and azoxymethane (AOM)-treated mice.
The RSPO fusions were mutually exclusive with APC mutations, indicating that they probably have a role in the activation of Wnt signalling and tumorigenesis.
Experiments were designed to assess the chemopreventive effects of a novel dual 5-LOX/COX inhibitor, licofelone {[6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl] acetic acid}, in APC(Min/+) mouse intestinal tumorigenesis.
Our results indicate that nuclear activation of β-catenin is a late event in the tumorigenesis of nephroblastomas coinciding in some tumours with LOH of the APC gene.
Our results indicate that de novo mutation or loss of heterozygosity in stromal APC is sufficient to induce endometrial hyperplasia and endometrial carcinogenesis by mechanisms that are consistent with unopposed estrogen signaling in the endometrial epithelium.
In contrast, in the mouse intestine, FAK activity was induced downstream of Wnt to promote intestinal regeneration and was also essential for tumorigenesis in an APC deletion model of colorectal cancer.
Furthermore, we found that adenomas bearing truncated Apc had increased beta-catenin activity when compared with tumors lacking Apc protein, which could lead to context-dependent inhibition of tumorigenesis.
Thus, APC mutation-induced up-regulation of the survivin/ABK cascade can explain delayed crypt cell maturation, expansion of proliferative cell populations (including mitotic figures), and promotion of colon tumorigenesis.
Alterations of APC, including loss of the entire locus, and CTNNB1 mutation could explain the tumorigenesis in 89% of sporadic desmoids tumors and desmoids tumors occurring in the context of Gardner's syndrome.
This review focuses on the roles of the APC and MMR genes in tumor development and the work that has been done to relate different variants in each gene to functional aberrations and ultimately tumorigenesis.
Because aberrant expression of beta-catenin might be associated with the epigenetic inactivation of WNT inhibitors, we analyzed, in a collection of primary OSCC with matched normal oral mucosa, the methylation status of a complete panel of genes, SFRP-1, SFRP-2, SFRP-4, SFRP-5, WIF-1, DKK-3, that are involved directly and indirectly in WNT pathway, in order to demonstrate WNT-pathway activation in the absence of beta-catenin and/or APC/Axin mutations during oral carcinogenesis.
We investigated methylation profiles of p16, LOX, HAND1, THBD, p41ARC, and APC along multistep gastric carcinogenesis and determined their association with Helicobacter pylori infection.
To further explore intestinal regional responses, we studied effects of sulindac on additional gene-targeted mouse models of human intestinal tumorigenesis; these were (i) Apc(1638N/+) mouse (chain termination mutation in exon 15 of the Apc gene); (ii) Mlh1(+/-) mouse (DNA mismatch repair deficiency, a mouse model of human hereditary non-polyposis colorectal cancer) and (iii) double-heterozygous Mlh1(+/-)Apc(1638N/+) mutant mouse.
Crossing APC(Min/+) with Jagged1(+/Delta) mice is sufficient to significantly reduce the size of the polyps arising in the APC mutant background indicating that Notch is an essential modulator of tumorigenesis induced by nuclear beta-catenin.