Claudin-1 is the direct target of RUNX3 in gastric epithelial cells

CHANG TI LING

Publication

Claudin-1 is the direct target of RUNX3 in gastric epithelial cells

CHANG TI LING

Abstract

The genes controlling cell-cell contact and cellular polarity are known to be heavily involved in cancer progression. Tumorigenic mouse GIF cells isolated from Runx3-/- gastric epithelium attached weakly to each other and did not form glandular structures on collagen gels as previously reported. In a search for RUNX3 target genes which play roles in gastric carcinogenesis, claudin-1 was found to be expressed at high level in Runx3+/+ gastric epithelial cells, but at very low level in Runx3-/- ones. TGF-o " induced expression of claudin-1 in SNU16, a human gastric cancer cell line. The TGF-o "-dependent expression of claudin-1, however, was not observed in RUNX3-knockdown SNU16 cells. In addition, hclaudin-1 promoter activity was up-regulated by the expression of RUNX3. The tumorigenicity of Runx3-/- GIF clones which stably expressed claudin-1 was significantly less than parental cell lines. Furthermore, claudin-1 and RUNX3 expression were found to be highly correlated in the human gastric cancers specimens. These results suggest the possible role of claudin-1 as a tumor suppressor, and its synergistic role with RUNX3 in the genesis of gastric cancer.