ER-α36 mediates gastric cancer cell invasion.

Estrogen evidently exerts a protective role against gastric cancer. Accordingly, we evaluated the relationship between the expression of the estrogen receptor ER-α36 and the clinicopathologic features in gastric cancer. ER-α36 expression levels differed among the tumor center, invasion front, and vascular metastases. The effects of E2β (17β-Estradiol, E2β) on invasion ability in SGC7901, High36 (with ER-α36 upregulation), and Low36 (with ER-α36 downregulation) cells were evaluated using Transwell assays. Furthermore, the c-Src signaling pathway was inhibited using PP2 and the effects on E2β-induced increases in E-cadherin, MMP2, and MMP9 were evaluated using western blotting. ER-α36, c-Src, MMP2, and E-cadherin levels were also evaluated in tumor xenografts. We found that 0.1 nM E2β promoted gastric cancer cell invasion by reducing E-cadherin expression and increasing MMP2 and MMP9 levels. The upregulation of ER-α36 promoted gastric cancer cell invasion and the downregulation of ER-α36 reduced the invasive ability of cells. The levels of ER-α36, c-Src, and MMP2 were the highest in tumor xenografts using High36 cells, intermediate in tumor xenografts using SGC7901 cells, and lowest in tumor xenografts using Low36 cells. The opposite results were obtained for E-cadherin expression. ER-α36 enhanced gastric cancer cell invasion by the activation of membrane-initiated c-Src signaling pathways. In particular, treatment with E2β and ER-α36 influenced gastric cancer cell invasion. Furthermore, c-Src was involved in the ER-α36-mediated estrogen signaling pathway and cell invasion.
Competing Interests: None.
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