Thus, we investigated the effect of MT1G on the p53 signaling pathways. As shown in Figure 5B, restoring tech support MT1G expression increased the activity and stability of p53, and the expression of its downstream targets, including p21, Bak and Smac, in K1 cells. However, this phenomenon was not found in FTC133 cells because TP53 gene is mutated in this cell line, leading to p53 in activation. These findings suggest that MT1G induces cell cycle arrest and apoptosis at least partially mediated by p53 signaling pathway. Collectively, MT1G inhibits thy roid cancer cell growth mainly through regulating PI3K Akt signaling pathway.

To explore the molecular mechanism of MT1G con tributing to thyroid cancer cell migration and invasion, we investigated the effect of MT1G on expression of E cadherin and Vimentin, the altered expressions of which are hallmarks of epithelial mesenchymal transition allowing epithelial cells to separate from their neighbors and migrate to distant regions during tumor development. As shown in Figure 5C, E cadherin expression was dramatically up regulated in the MT1G transfected cells compared with empty vector transfected cells. However, Vimentin expression was not significantly influenced by MT1G restoration. Additionally, we determined the mRNA expression of E cadherin, Vimentin, and the tran scription suppressors of E cadherin, including Snail, Slug, and Twist in K1 and FTC133 cells. As shown in, the expression of these genes was not significantly different between MT1G transfected cells and empty vector transfected cells, suggesting that MT1G regulated E cadherin expres sion at the post transcriptional level.

Taken together, our data suggest that MT1G inhibits cell migration and invasion by increasing the stability of E cadherin. Notably, we observed that MT1G slightly inhibited phosphorylation of tumor suppressor Rb, which plays a key role in regulating cell cycle and cell death, in the MT1G transfected cells as compared to empty vector transfected cells, suggesting that MT1G might play a role in the control of cell proliferation partially through modulating the activity of Rb E2F pathway. Discussion In the present study, we found that MT1G expression was frequently absent or down regulated in thyroid can cer cell lines, and was also significantly decreased in pri mary thyroid cancer tissues compared with non malignant thyroid tissues, which was consistent with the previous studies.

These findings suggested that MT1G would be a candidate tumor suppressor in the pathogenesis of thyroid cancer. The reduced expression of MT1G is closely associated with promoter methylation, as confirmed by MSP assays and pharmacological DNA demethylation treatment selleck chemicals Tofacitinib in the present study and a previous study, implicating DNA methylation as a regulatory mechanism of MT1G inactivation in thyroid cancer.