The lipid metabolism gene FTO influences breast cancer cell energy metabolism via the PI3K/Akt signaling pathway

Liu,Yazhuo; Wang,Ruoyu; Zhang,Lichuan; Li,Jianhua; Lou,Keli; Shi,Bingyin

doi:10.3892/ol.2017.6038

The lipid metabolism gene FTO influences breast cancer cell energy metabolism via the PI3K/Akt signaling pathway

Authors:
- Yazhuo Liu
- Ruoyu Wang
- Lichuan Zhang
- Jianhua Li
- Keli Lou
- Bingyin Shi
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Affiliations: Department of Metabolic Diseases and Nutritional Disorders, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning 116001, P.R. China, Department of Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning 116001, P.R. China, Department of Respiratory Medicine, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning 116001, P.R. China, Department of Nursing, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning 116001, P.R. China, Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
Published online on: April 13, 2017 https://doi.org/10.3892/ol.2017.6038
Pages: 4685-4690
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study assessed the effect of the lipid metabolism, fat mass and the obesity‑associated gene (FTO), on energy metabolism of breast cancer cells. The human breast cancer cell lines, MCF-7 and MDA-MB-231, and HCC1937 human breast cells were studied. Real-time PCR was used to measure the levels of FTO mRNA from breast cancer cells and normal breast cells. MDA-MB‑231 cells were transfected with miFTO inhibitor or inhibitor control, and cells were assessed for levels of lactic acid, ATP, pyruvate kinase activity, and hexokinase activity assay using specific kits. Western blot analysis was used to measure the levels of phosphatidylinositol 3-kinase (PI3K), p-PI3K, protein kinase B (Akt) and p-Akt in transfected breast cancer cells. The expression of FTO was significantly increased in MCF-7 and MDA-MB‑231 cells compared with HCC1937 cells (P<0.01). The lactic acid content of breast cancer cells transfected with the miFTO inhibitor was significantly lower compared with cells transfected with the miFTO inhibitor control and nontransfected cells (P<0.05). The ATP content of breast cancer cells transfected with the miFTO inhibitor was significantly lower compared with the control group and inhibitor control group (P<0.05). The pyruvate kinase activity and hexokinase activity of breast cancer cells transfected with the miFTO inhibitor were significantly lower compared with the control group and inhibitor control group (P<0.01). Western blot analysis showed that after breast cancer cells were transfected with the miFTO inhibitor, the levels of PI3K, p-PI3K, Akt and p-Akt were significantly lower than in the control group and inhibitor control group. In conclusion, the FTO gene is overexpressed in breast cancer cells. Overexpression of the FTO gene can promote breast cancer cell glycolysis and the mechanism is related to the PI3K/Akt signaling pathway.

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