Upregulation of estrogen receptor mediates migration, invasion and proliferation of endometrial carcinoma cells by regulating the PI3K/AKT/mTOR pathway

The precise mechanism through which the two estrogen receptor subtypes, ER and ER, are linked to endometrial malignant progression is not fully understood. The aim of the present study was to examine their role in endometrial carcinoma cell migration, invasion and proliferation. We also explored the correlation between the ERs and phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathways in endometrial carcinoma cells. Using Ishikawa and KLE cells as model systems, we performed transient transfection to upregulate ER and ER expression; fluorescence microscopy analysis was then employed to evaluate transfection efficiencies, RT-PCR and western blot assays were used to evaluate the mRNA and protein levels. We further examined the effects on cell migration, invasion and proliferation. We showed that ER raised the phosphorylation levels of PI3K p85, activated the phosphorylation of AKT and mTOR in Ishikawa and KLE cells, but ER had no effect on PI3K p85 phosphorylation. Moreover, the overexpression of ERs enhanced cell migration, invasion and proliferation. The effect on the activation of the PI3K/AKT/mTOR transduction cascade by ER explains, at least in part, the enhancement on cell invasion and proliferation exerted by overexpression of ER. This crosstalk could be taken into account in developing novel therapeutic methods by targeting the ER and PI3K/AKT/mTOR pathways in endometrial carcinoma.