FEATURES OF CDH1, CTNNB1 GENES TRANSCRIPTIONAL ACTIVITY AND EXPRESSION LEVELS OF E-CADHERIN, Β-CATENIN PROTEINS CODED BY THESE GENES ON THE I, II, III, IV STAGES OF COLORECTAL ADENOCARCINOMA DEVELOPMENT
Aim - analysis of CDH1 and CTNNB1 genes mRNA expression levels and expression levels of E-cadherin, β-catenin proteins coded by these genes, and also their correlations with KRAS gene transcriptional activity level on the I, II, III, IV stages (pTNM) of colorectal adenocarcinoma (CRA) development. Materials and methods. Parallel immunohistochemical and molecular-genetic, pathohistological studies of operational material of CRA from 40 patients (4 study groups - I, II, III, IV stages according to pTNM classification - 10 cases in each group) with diagnosis of colorectal adenocarcinoma, and sectional material of 10 fragments of distal colonic wall with normal histological structure were conducted. Results. In comparison with unchanged mucosa of distal colon CRA is characterized by the decreased CDH1 gene transcriptional activity. There is the tendency to reducing of CDH1 gene mRNA expression in the study groups - from the I to the IV stages of the tumor development. CRA is characterized by the low E-cadherin expression level, which also has the tendency to reducing in the study groups. Moreover, in comparison with unchanged mucosa of distal colon CRA is characterized by the increased CTNNB1 gene transcriptional activity and the high β-catenin expression level. There aren’t statistically significant differences between the CTNNB1 gene mRNA, β-catenin expression levels in the study groups. There are direct correlations between the expression levels of the studied genes and the molecules, coded by these genes, and also reverse correlations between the KRAS and CDH1 genes mRNA expression levels, the KRAS gene mRNA expression level and the E-cadherin expression level, direct correlation between the KRAS gene mRNA expression level and the β-catenin expression level. Conclusions. CRA is characterized by the decreased CDH1 gene transcriptional activity that correlates with the low E-cadherin expression level, and by the increased CTNNB1 gene transcriptional activity that correlates with the high β-catenin expression level. The CDH1 gene transcriptional activity and the expression level of E-cadherin, which is coded by this gene, decrease during the CRA progression from the I to the IV stages. CRA is characterized by reverse correlations between the KRAS and CDH1 genes mRNA expression levels, the KRAS gene mRNA expression level and the E-cadherin expression level, direct correlation between the KRAS gene mRNA expression level and the β-catenin expression level.