title: Knockdown of dual specificity phosphatase 4 enhances the chemosensitivity of MCF-7 and MCF-7/ADR breast cancer cells to doxorubicin.
abstract: BACKGROUND
  Breast cancer is the major cause of cancer-related deaths in females world-wide. Doxorubicin-based therapy has limited efficacy in breast cancer due to drug resistance, which has been shown to be associated with the epithelial-to-mesenchymal transition (EMT). However, the molecular mechanisms linking the EMT and drug resistance in breast cancer cells remain unclear. Dual specificity phosphatase 4 (DUSP4), a member of the dual specificity phosphatase family, is associated with cellular proliferation and differentiation; however, its role in breast cancer progression is controversial.
  
  
  METHODS
  We used cell viability assays, Western blotting and immunofluorescent staining, combined with siRNA interference, to evaluate chemoresistance and the EMT in MCF-7 and adriamycin-resistant MCF-7/ADR breast cancer cells, and investigate the underlying mechanisms.
  
  
  RESULTS
  Knockdown of DUSP4 significantly increased the chemosensitivity of MCF-7 and MCF-7/ADR breast cancer cells to doxorubicin, and MCF-7/ADR cells which expressed high levels of DUSP4 had a mesenchymal phenotype. Furthermore, knockdown of DUSP4 reversed the EMT in MCF-7/ADR cells, as demonstrated by upregulation of epithelial biomarkers and downregulation of mesenchymal biomarkers, and also increased the chemosensitivity of MCF-7/ADR cells to doxorubicin.
  
  
  CONCLUSIONS
  DUSP4 might represent a potential drug target for inhibiting drug resistance and regulating the process of the EMT during the treatment of breast cancer.
authors.affiliation: Department of Breast Surgery Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Feiya
authors.initials: F
authors.lastname: Du
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Minya
authors.initials: M
authors.lastname: Yao
authors.forename: Kezhen
authors.initials: K
authors.lastname: Lv
authors.forename: Peifen
authors.initials: P
authors.lastname: Fu
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D054637:Dual-Specificity Phosphatases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; D012333:RNA, Messenger; D004317:Doxorubicin; D054639:Mitogen-Activated Protein Kinase Phosphatases; C490583:DUSP4 protein, human; D054637:Dual-Specificity Phosphatases
keywords: 4,6-diamidino-2-phenylindole; Breast cancer; CCK-8; Chemoresistance; DAPI; DUSP4; Doxorubicin; EMT; MAP; PBS; TGF-β; cell counting kit-8 assay; dual specificity phosphatase 4; epithelial-to-mesenchymal transition; mitogen-activated protein; phosphate buffer solution; transforming growth factor beta