Therefore, we tested whether a similar preparation might reduce tumorigenesis in the colon of Pirc rats (F344/NTac-Apc) mutated in the Apc gene and thus, like familial adenomatous polyposis patients, spontaneously developing multiple tumors in the colon.
GSEA demonstrated a strong association between duodenal adenoma/adenocarcinomas with colorectal adenomas (p < 10<sup>-5</sup>) and gene expression patterns seen after APC gene knockout (p < 10<sup>-5</sup>), suggesting that the Wnt/β-catenin pathway plays a crucial role in the carcinogenesis of these neoplasms.
In contrast, intestinal tumorigenesis was not suppressed by Stat3 disruption in adenomatous polyposis coli ( Apc) <sup>Δ716</sup> and Apc<sup>∆716</sup> Tgfbr2<sup>∆IEC</sup> mice, thus indicating that Stat3 is not required for Wnt activation-driven intestinal tumorigenesis.
Genetic deletion of the IL-1 receptor (IL-1R1) in epithelial cells alleviated tumorigenesis in the APC model of CRC, demonstrating a cell-autonomous role for IL-1 signaling in early tumor seed outgrowth.
Our results demonstrated that metabolites alterations in FAP can be helpful for further analysis of metabonomics induced by APC mutation, and these alterations might be involved in the progress of intestinal carcinogenesis.
In the current study, we found that NHP inhibited colorectal tumorigenesis in the APC <sup>min/+</sup> transgenic mouse model, as well as induced apoptosis and blocked angiogenesis in vivo.
But the age of carcinogenesis for patients with both APC and MUTYH mutations was later than APC mutation carriers and similar to MUTYH mutation carriers.
In contrast to this well-established role of APC, recent studies from our laboratory demonstrated that APC functions through Wnt-independent pathways to mediate in vitro and in vivo models of breast tumorigenesis.
Hereditary polyposis syndromes in which APC gene germline mutations can lead to colorectal carcinogenesis are familial adenomatous polyposis (FAP), attenuated FAP (AFAP) and MUTYH-associated polyposis.
In this study, we investigated the effects of pentoxifylline on inflammation-related colon tumorigenesis in a rodent model using Kyoto APC delta rats, which have APC mutation and are susceptible to colon carcinogenesis.
We conclude that increased WNT signaling is important in the transition to malignancy in the serrated pathway but that APC mutation is less common and the spectrum of mutations is different than in conventional colorectal carcinogenesis.
The study aims to provide deeper insights into the discovery, identification and functional pathways analysis of differentially expressed metabolites in intestinal tumorigenesis in APC <sup>min/+</sup> mice used by the serum metabolomics, and bring about useful information for further effective prevention and treatment of the disease.
The Apc<sup>Min/+</sup> mouse, carrying an inactivated allele of the adenomatous polyposis coli (Apc) gene, is a widely used animal model of human colorectal tumorigenesis.
Based on published and our data we propose that K-ras could be the oncogene responsible for the inactivation of the tumor-suppressor gene APC, currently considered as the initial step in colorectal tumorigenesis.
In conclusion, we have developed a novel iPSC/intestinal model of APC mutagenesis and provide strong evidence that APC in heterozygosity imparts a clear phenotypic and molecular defect, affecting basic cellular functions and integrity, providing novel insights in the earlier events of APC-mediated tumorigenesis.
Our findings therefore reveal a reciprocal suppression mechanism between FZR1 and BRAF in controlling tumorigenesis.<b>Significance:</b> FZR1 inhibits BRAF oncogenic functions via both APC-dependent proteolysis and APC-independent disruption of BRAF dimers, whereas hyperactivated ERK and CDK4 reciprocally suppress APC<sup>FZR1</sup> E3 ligase activity.
This novel Wnt-driven mammary tumor model highlights the importance of functional redundancies existing between the Apc proteins both in normal homeostasis and in tumorigenesis.
Together, our results suggest that the high-risk Western diet primes the intestine to tumorigenesis through synergistic effects in energy metabolism, inflammation and oxidative stress, which culminate in the acceleration of LOH of the Apc gene.
The results indicate that APC promoter hypermethylation is an early event in carcinogenesis of CRC, could be a valuable diagnostic marker for early-stage CRC.
The proportion of APC promoter 1A methylation in lung cancer tissues was higher than in autologous controls, indicating that promoter 1A methylation of the APC gene may play an important role in NSCLC carcinogenesis.