Wnt/β-catenin gene expression in colon adenomas and adjacent colonic mucosa

BACKGROUND. The importance of canonical Wnt/β-catenin signalling for colon development and cancer progression has long been recognised. Adenomatous polyposis coli (APC) gene, a Wnt component, contributes to adenoma formation but some its roles remain to elucidate. Transcript dosage may influence transcriptome. To elucidate the role of altered gene expression in colon adenomas we analyzed APC and other components of Wnt pathways. MATERIALS AND METHODS. Patients with familial and sporadic polyps were enrolled following inclusion (age! 18 years) and exclusion (inflammatory bowel diseases) criteria. Donors with no family history of cancer were recruited as controls. mRNA expression levels were investigated by quantitative Real- Time PCR (qRT-PCR). The correlation among clinical and molecular features has been evaluated. RESULTS. We analyzed expression in colon tumour tissues (n. 26), adjacent mucosa (n.19) from 11 patients with FAP (familial adenomatous polyposis) and 25 with sporadic adenomas , and in normal colonic mucosa from 12 healthy controls. qRT-PCR results showed a reduced APC expression in colon tumour tissues (0.15 2- ΔCT) as compared to the adjacent mucosa (0.32 2-ΔCT). Intriguingly the APC expression in adjacent colonic mucosa was higher also compared to healthy controls colonic mucosa. The differences in APC expression between colon tumour tissues and adiacent mucosa in familial and sporadic cases, were statistically significant in familial group (p=0.0054). We also correlated APC expression with age. In patients the expression levels tend to decrease more rapidly with age. Instead in control group there is a constant APC expression trend in life. Correlation with sex showed that the APC reduced expression is more evident in men than female. Downstream Wnt/-catenin components BCL9 and LEF1 showed a reduced expression in adjacent colonic mucosa vs adenomas in cases analyzed. Expression analysis of Wnt ligands is in progress. CONCLUSIONS. This study showed that the APC gene is lower expressed in colon tumor tissue compared to the adjacent mucosa but more expressed in adjacent mucosa compared to mucosa of healthy controls. The increased APC expression in adjacent mucosa could be due to a cross talk between tumor and surrounding colonic epithelium.