Abstract
Colorectal cancer (CRC) is among the most common and fatal forms of solid tumors worldwide and more than two thirds of CRC and adenomas patients have APC gene mutations. APC is a key regulator in the Wnt/β-catenin signaling pathway but its roles in CRC remains to be elucidated. In this study, we compared APC genes between CRC patients and controls to determine possible associations of nucleotide changes in the APC gene with the pathways involved in CRC pathogenesis. All participants received physical and enteroscopic examinations. The APC gene was sequenced for 300 Chinese Han CRC patients and 411 normal controls, and the expression levels of genes in the signaling pathway were analyzed using Western Blotting. Statistical analyses were conducted using SPSS (version 19.0) software. We found that rs11954856 in the APC gene was associated with colorectal cancer and could increase the expression levels of APC, β-catenin, TCF7L1, TCF7L2 and LEF1 genes in the pathway in the CRC patients, demonstrating the involvement of APC in the pathological processes leading to CRC.
Highlights
Colorectal cancer (CRC) is one of the most common and fatal forms of solid tumors in both men and women [1, 2]
We found that rs11954856 in the adenomatous polyposis coli (APC) gene was associated with colorectal cancer and could increase the expression levels of APC, β-catenin, TCF7L1, TCF7L2 and LEF1 genes in the pathway in the CRC patients, demonstrating the involvement of APC in the pathological processes leading to CRC
Multiple mutations concurrently appearing in a gene may result in marked predisposition to CRC, such as those in the adenomatous polyposis coli (APC) gene, which is associated with familial adenomatous polyposis disease (FAP) [15]
Summary
Colorectal cancer (CRC) is one of the most common and fatal forms of solid tumors in both men and women [1, 2]. We identified a novel mutation (p.1125Val>Ala) in the APC gene, which is associated with FAP and sporadic cases of CRC [32]. We profiled nucleotide changes of the APC gene and found that the SNP rs11954856 was associated with CRC This SNP increased expression levels of genes in the Wnt/β-catenin signaling pathway in the CRC cancer patients, including APC, β-catenin, and transcription factor genes TCF7L1, TCF7L2, LEF1 in the pathway. The p.1125Val>Ala mutation of the APC gene in the CRC cancer patients increased expression levels of genes downstream of APC in the Wnt/β-catenin signaling pathway and a gene upstream of APC, GSK-3β, for feedback, providing further evidence indicating the involvement of the APC gene in the pathogenesis of CRC
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