TGF-β1-induced expression of Id-1 is associated with tumor progression in gastric cancer

Transforming growth factor beta 1 (TGF-beta 1) and inhibitor of differentiation/DNA-binding 1 (Id-1) have been shown to be associated with aggressive metastatic behavior of cancer cells in many malignant tumors. However, their role in gastric cancer (GC) has not been established. In this study, we investigated the relationship between expression of Id-1 and TGF-beta 1 in GC as well as their association with GC progression. The immunohistochemical analysis of 71 human GC samples indicated that both Id-1 and TGF-beta 1 were markedly upregulated in tumor tissue compared with the adjacent tissue; in addition, a significant positive correlation was found between the expression levels of Id-1 and TGF-beta 1 by Pearson's correlation analysis. Furthermore, the investigation of the association of Id-1 and TGF-beta 1 with patient clinical characteristics revealed that Id-1 expression was significantly correlated with tumor differentiation, while TGF-beta 1 was associated with lymph node metastasis. The results were validated in vitro by using a GC cell line, AGS. The expression of Id-1 was upregulated at 24 and 48 h after the treatment with TGF-beta 1, whereas it did not affect the proliferation of cells. TGF-beta 1 also influenced the expression of N-cadherin and beta-catenin. Our results suggested that Id1 and TGF-beta 1 played important roles in the progression of GC, in which Id-1 might act as a downstream mediator of TGF-beta 1 signaling through a regulatory mechanism involving N-cadherin and beta-catenin. The TGF-beta 1/Id-1 axis might serve as a future therapeutic target for GC.