Gene Set: LIU_CDX2_TARGETS_UP

Standard name LIU_CDX2_TARGETS_UP
Systematic name M16637
Brief description Genes up-regulated in HET1A cells (esophagus epithelium) engineered to stably express CDX2 [GeneID=1045].
Full description or abstract Caudal-related homeobox 2 (Cdx2) has been suggested as an early marker of Barrett's esophagus (BE), which is the premalignant lesion of esophageal adenocarcinoma (EAC). However, the mechanism of ectopic Cdx2 expression in the esophageal epithelial cells and its role in the development of BE remained unclear. RT-PCR, pyrosequencing and methylation-specific PCR were used to determine expression and promoter methylation of Cdx2 in human esophageal epithelial cells (HET1A and SEG1) after treatment with 5-aza-2'-deoxycytidine (DAC), acid, bile acids and their combination. HET1A cells with stable transfection of Cdx2 were characterized for morphology and gene expression profiles with Affymetrix array. We found Cdx2 was expressed in most human EAC cell lines, but not in squamous epithelial cell lines. DAC-induced demethylation and expression of Cdx2 in HET1A and SEG1 cells, and treatment with a DNA methylating agent counteracted the effect of DAC. Treatment of HET1A and SEG1 cells with acid, bile acids or both also resulted in promoter demethylation and expression of Cdx2. HET1A cells with stable transfection of human Cdx2 formed crypt-like structures in vitro. Microarray analysis and quantitative real-time PCR showed that stable transfection of Cdx2 up-regulated differentiation markers of intestinal columnar epithelial cells and goblet cells in HET1A cells. This may be partially due to modulation of Notch signaling pathway, as western blotting confirmed down-regulation of Hes1 and up-regulation of Atoh1 and Muc2. Our data suggest that exposure to acid and/or bile acids may activate Cdx2 expression in human esophageal epithelial cells through promoter demethylation, and ectopic Cdx2 expression in esophageal squamous epithelial cells may contribute to intestinal metaplasia of the esophagus.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 16990345   Authors: Liu T,Zhang X,So CK,Wang S,Wang P,Yan L,Myers R,Chen Z,Patterson AP,Yang CS,Chen X
Exact source Table 1
Related gene sets (show 1 additional gene sets from the source publication)

(show 410 gene sets from the same authors)
External links  
Organism Homo sapiens
Contributed by Arthur Liberzon (Broad Institute)
Source platform HG-U133A
Dataset references  
Download gene set format: grp | text | gmt | gmx | xml
Compute overlaps (show collections to investigate for overlap with this gene set)
Compendia expression profiles Human tissue compendium (Novartis)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 36 genes
Gene families Categorize these 36 genes by gene family
Show members (show 36 members mapped to 36 genes)
Version history 3.0: First introduced

See MSigDB license terms here. Please note that certain gene sets have special access terms.