The expression levels of the transcriptional regulators p300 and CtBP modulate the correlations between SNAIL, ZEB1, E-cadherin and vitamin D receptor in human colon carcinomas


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Abstract

ZEB1 and SNAIL repressCDH1and induce epithelial–mesenchymal transition (EMT). However, SNAIL and ZEB1 also activate or regulate other target genes in different ways. For instance, vitamin D receptor (VDR), which activatesCDH1expression upon ligand binding, is repressed by SNAIL but induced by ZEB1. We examined whether the biological activity of SNAIL and ZEB1 in colon cancer is regulated by interacting cofactors. The mRNA expression levels ofSNAILandZEB1, and of transcriptional regulatorsp300andCtBP,were measured by RT-PCR in tumor and normal tissue from 101 colon carcinoma patients. Overexpression ofSNAILwas associated with down-regulation ofCDH1andVDR(p= 0.004 andp< 0.001).CDH1correlated withVDR(r= 0.49;p< 0.001).ZEB1expression also correlated withVDR(r= 0.23;p= 0.019). However, whenCtBPwas strongly expressed,ZEB1was inversely correlated withCDH1(r= −0.39;p= 0.053). Furthermore, when there were elevatedp300expression levels, the correlation between expression ofZEB1andVDRwas stronger (r= 0.38;p= 0.070). Association betweenSNAILexpression and down-regulation ofCDH1andVDRwas lost in tumors in whichp300andCtBPwere strongly expressed. These results indicate that the levels of expression of CtBP and p300 are critical for the action of SNAIL and ZEB1, which have a pivotal role in EMT, and show the importance of CtBP and p300 for tumor progression.

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