Estrogen promotes fat mass and obesity-associated protein nuclear localization and enhances endometrial cancer cell proliferation via the mTOR signaling pathway

Zhu,Yaping; Shen,Jiaqi; Gao,Liyan; Feng,Youji

doi:10.3892/or.2016.4613

Estrogen promotes fat mass and obesity-associated protein nuclear localization and enhances endometrial cancer cell proliferation via the mTOR signaling pathway

Authors:
- Yaping Zhu
- Jiaqi Shen
- Liyan Gao
- Youji Feng
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Affiliations: Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai 200080, P.R. China
Published online on: February 5, 2016 https://doi.org/10.3892/or.2016.4613
Pages: 2391-2397

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Abstract

Extensive exposure to estrogen is generally acknowledged as a risk factor for endometrial cancer. Given that the accumulation of adipocytes also contributes to the increased production of estrogen, in the present study, we evaluated the expression of the fat mass and obesity-associated (FTO) gene in endometrial tumor tissues and further explored the mechanism of how estrogen facilitates FTO nuclear localization and promotes endometrial cancer cell proliferation. Immunohistochemical (IHC) staining assay was used to detect the FTO expression in endometrial tumor samples. Western blotting was performed to investigate the mechanism of estrogen-induced FTO nuclear localization. siRNA was used to knock down ERα and further explore its role in FTO nuclear localization. MTT assay was carried out to determine cell proliferation. We found that FTO was overexpressed in endometrial carcinoma tissues and served as a poor prognostic marker. Additionally, estrogen induced FTO nuclear accumulation via the mTOR signaling pathway and the nuclear localization was ERα-dependent, which contributed to enhanced proliferative activity. Therefore, the present study provides new insight into the mechanisms of estrogen-induced proliferation, implying the possibility of using FTO as a potential therapeutic target for the treatment of endometrial cancer.

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