Most sporadic DTs are associated with β-catenin gene (CTNNB1) mutations, while mutated APC gene causes FAP disease. microRNAs (miRNAs) are involved in many human carcinogenesis.The miRNA profile was analyzed by microarray in formalin-fixed, paraffin-embedded (FFPE) specimens of 12 patients (8 sporadic, 4 FAP-associated) and 4 healthy controls.
Our findings provide exploratory evidence for hypermethylation of the key tumour suppressor gene APC being implicated in smoking-associated colorectal carcinogenesis.
Regarding the relationship between COX-2 and cancer related proteins, we found that COX-2 expression is positively associated with APC (p = 0.006), and P53 (p = 0.026), supporting a cross link between these proteins in gastric carcinogenesis.
APC (80-90%) and K-Ras (40-50%) mutations frequently occur in human colorectal cancer (CRC) and these mutations cooperatively accelerate tumorigenesis including metastasis.
LOI of IGF2 is a frequent and early event in CRC that occurs both in the adenomatous polyposis coli (APC) gene-mutated and serrated route of carcinogenesis.
These findings suggest that biallelic functional APC inactivation initiates the gastric carcinogenesis and is followed by mutations of histone modifiers and then activation of known cancer-related genes.
The most commonly initiating event of intestinal carcinogenesis is mutation of the adenomatous polyposis coli (APC) gene, which leads to activation of the Wnt/β-catenin pathway.
Nevertheless, deficiency of IL-17A but not RORγt is associated with decreased spontaneous intestinal tumorigenesis in the APC(MIN/+) mouse model, despite the fact that helper T cells from RORγt-deficient APC(MIN/+) mice do not secrete IL-17A when subjected to Th17-polarizing conditions and that Il17a expression is decreased in the intestine of RORγt-deficient APC(MIN/+) mice.
There was no difference in the rate of tumor formation of CDX2P9.5-G19Cre;Apc(flox/flox) and CDX2P9.5-G22Cre;Apc(flox/flox) mice consuming chlorinated as compared to tap water, suggesting that microsatellite instability in the Apc gene does not significantly affect tumorigenesis.
Although β-catenin and adenomatous polyposis coli (APC) gene mutations are well established and are known to drive tumorigenesis, discoveries of mutations in other components of the pathway lagged, which hinders the understanding of cancer mechanisms.
Well-known genetic bases for the carcinogenesis of CRC include chromosomal changes characteristic of the chromosomal instability pathway which correlates with specific and well-defined genetic alterations (such as APC, K-RAS, DCC and p53) and genomic instability characteristics for the mutator pathway focused on KRAS and BRAF mutations.
Finally, we discuss future research directions to further elucidate the physiological contributions of APC/C components during tumorigenesis and validate their potentials as a novel class of anti-cancer targets.
In our study, promoter methylation which was considered to be occurred as an early event in gastrointestinal carcinogenesis was observed in p16 and APC genes.
Notably, the concomitant loss of Cdx1 led to a significant increase in the incidence of tumors in the distal colon, relative to APC(Min/+)-Cdx2 offspring, demonstrating a previously unrecognized role for this transcription factor in colorectal tumorigenesis.
For the initiation of oncogenesis however, one or more additional molecular alterations must occur, such as a new somatic mutation in the APC gene (biallelic inactivation), somatic mutations in the β-catenin (CTNNB1) gene, or gene-gene interaction (epistasis).
Cell division cycle 20 (CDC20) encodes a regulatory protein interacting with the anaphase-promoting complex/cyclosome (APC/C) in the cell cycle and plays important roles in tumorigenesis and progression of multiple tumors.
Colorectal tumorigenesis is ascribed to the activity of Wnt signaling pathway in a ligand-independent manner mainly through APC and CTNNB1 gene mutations and in a ligand-dependent manner through low expression of Wnt inhibitors such as WNT inhibitory factor 1 (WIF1) and secreted frizzled related protein 1 (SFRP1).