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

Hou,Xinxin; Zhao,Meng; Wang,Tong; Zhang,Guiyu

doi:10.3892/or.2013.2944

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

Authors:
- Xinxin Hou
- Meng Zhao
- Tong Wang
- Guiyu Zhang
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Affiliations: Department of Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China, Department of Neurosurgery, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China
Published online on: December 23, 2013 https://doi.org/10.3892/or.2013.2944
Pages: 1175-1182

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Abstract

The precise mechanism through which the two estrogen receptor subtypes, ERα and ERβ, 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 ERα and ERβ 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 ERα raised the phosphorylation levels of PI3K p85α, activated the phosphorylation of AKT and mTOR in Ishikawa and KLE cells, but ERβ had no effect on PI3K p85α 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 ERα explains, at least in part, the enhancement on cell invasion and proliferation exerted by overexpression of ERα. This crosstalk could be taken into account in developing novel therapeutic methods by targeting the ERα and PI3K/AKT/mTOR pathways in endometrial carcinoma.

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