Liverâintestine cadherin induction by epidermal growth factor receptor is associated with intestinal differentiation of gastric cancer
Open Access
- 7 June 2012
- journal article
- research article
- Published by Wiley in Cancer Science
- Vol. 103 (9), 1744-1750
- https://doi.org/10.1111/j.1349-7006.2012.02353.x
Abstract
Gastric cancer (GC) is one of the most common malignancies worldwide. The epidermal growth factor receptor (EGFR) molecule is very important in GC progression. To examine the correlation between EGFR and GCârelated genes, we analyzed gene expression profiles of HTâ29 cells treated with EGFR ligands and identified six genes upregulated by epidermal growth factor (EGF) and transforming growth factor (TGF)âα treatment. Among these, we focused on cadherin 17 (CDH17) encoding liverâintestine cadherin (LIâcadherin). Expression of LIâcadherin was induced by both EGF and TGFâα, as detected by quantitative RTâPCR and Western blot analysis. A luciferase assay showed that LIâcadherin promoter activity was enhanced by EGF or TGFâα in both HTâ29 cells and MKNâ74 GC cells. Immunohistochemical analysis of 152 GC cases showed that out of 58 LIâcadherinâpositive cases, 24 (41%) cases were also positive for EGFR, whereas out of 94 LIâcadherinânegative cases, only 9 (10%) cases were positive for EGFR (P < 0.0001). Doubleâimmunofluorescence staining revealed that EGFR and LIâcadherin were coexpressed. Significant correlation was found between LIâcadherin expression and advanced T grade and N grade. Both EGFR and LIâcadherin expression were more frequently found in GC cases with an intestinal mucin phenotype than in cases with a gastric mucin phenotype. These results indicate that, in addition to the known intestinal transcription factor caudal type homeobox 2, EGFR activation induces LIâcadherin expression and participates in intestinal differentiation of GC.Keywords
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