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http://dx.doi.org/10.7314/APJCP.2014.15.18.7617

Mechanism of Fatty Acid Synthase in Drug Tolerance Related to Epithelial-mesenchymal Transition of Breast Cancer  

Li, Jun-Qin (Department of Anatomy, School of Basic and Forensic Medicine, Sichuan University)
Xue, Hui (Department of Anatomy, School of Basic and Forensic Medicine, Sichuan University)
Zhou, Lan (Department of Anatomy, School of Basic and Forensic Medicine, Sichuan University)
Dong, Li-Hua (Department of Anatomy, School of Basic and Forensic Medicine, Sichuan University)
Wei, Da-Peng (Department of Anatomy, School of Basic and Forensic Medicine, Sichuan University)
Li, Hua (Department of Anatomy, School of Basic and Forensic Medicine, Sichuan University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.18, 2014 , pp. 7617-7623 More about this Journal
Abstract
Objective: The mechanism of action of fatty acid synthase (FASN) in drug tolerance of breast cancer cells with epithelial-mesenchymal transition (EMT) features was investigated. Methods: The breast cancer cell line MCF-7-MEK5 with stably occurring EMT and tumour necrosis factor-${\alpha}$ (TNF-${\alpha}$) tolerance was used as the experimental model, whereas MCF-7 acted as the control. Tumour cells were implanted into nude mice for in vivo analysis, and cerulenin was used as a FASN inhibitor. RT-PCR, real-time quantitative PCR and Western blot were employed to detect the expression of FASN, TNFR-1, TNFR-2, Wnt-1, ${\beta}$-catenin and cytC at the RNA and protein levels. Results: Compared with MCF-7, TNFR-1 expression in MCF-7-MEK5 was slightly changed, TNFR-2 was decreased, and FASN, Wnt-1, ${\beta}$-catenin and cytC were increased. The expression of Wnt-1 and ${\beta}$-catenin in MCF-7-MEK5 decreased after cerulenin treatment, whereas cytC expression increased. Conclusions: The important function of FASN in the drug tolerance of breast cancer may be due to the following mechanisms: FASN downregulated TNFR-2 expression through lipid rafts to make the cells less sensitive to TNF-${\alpha}$, and simultaneously activated the Wnt-$1/{\beta}$-catenin signalling pathway. Thus, cytC expression increased, which provided cells with anti-apoptotic capacity and induced drug tolerance.
Keywords
Breast cancer; EMT; FASN; TNF-${\alpha}$; TNFR; Wnt; $1/{\beta}$; catenin;
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