title: Mechanism of fatty acid synthase in drug tolerance related to epithelial-mesenchymal transition of breast cancer.
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-α (TNF-α) 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, β-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, β-catenin and cytC were increased. The expression of Wnt-1 and β-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-α, and simultaneously activated the Wnt-1/β-catenin signalling pathway. Thus, cytC expression increased, which provided cells with anti-apoptotic capacity and induced drug tolerance.
authors.affiliation: Department of Anatomy, School of Basic and Forensic Medicine, Sichuan University, Chengdu, China E-mail : lihua_scu@scu.edu.cn.
authors.forename: Jun-Qin
authors.initials: JQ
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Xue
authors.forename: Lan
authors.initials: L
authors.lastname: Zhou
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Dong
authors.forename: Da-Peng
authors.initials: DP
authors.lastname: Wei
authors.forename: Hua
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D004361:Drug Tolerance; D058750:Epithelial-Mesenchymal Transition; D054890:Fatty Acid Synthase, Type I / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D060888:Real-Time Polymerase Chain Reaction; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D060449:Wnt Signaling Pathway / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D045304:Cytochromes c; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I