title: Molecular Modification of Metadherin/MTDH Impacts the Sensitivity of Breast Cancer to Doxorubicin.
abstract: BACKGROUND
  Breast cancer is a leading cause of death in women and with an increasing worldwide incidence. Doxorubicin, as a first-line anthracycline-based drug is conventional used on breast cancer clinical chemotherapy. However, the drug resistances limited the curative effect of the doxorubicin therapy in breast cancer patients, but the molecular mechanism determinants of breast cancer resistance to doxorubicin chemotherapy are not fully understood. In order to explore the association between metadherin (MTDH) and doxorubicin sensitivity, the differential expressions of MTDH in breast cancer cell lines and the sensitivity to doxorubicin of breast cancer cell lines were investigated.
  
  
  METHODS
  The mRNA and protein expression of MTDH were determined by real-time PCR and Western blot in breast cancer cells such as MDA-MB-231, MCF-7, MDA-MB-435S, MCF-7/ADR cells. Once MTDH gene was knocked down by siRNA in MCF-7/ADR cells and overexpressed by MTDH plasmid transfection in MDA-MB-231 cells, the cell growth and therapeutic sensitivity of doxorubicin were evaluated using MTT and the Cell cycle assay and apoptosis rate was determined by flow cytometry.
  
  
  RESULTS
  MCF-7/ADR cells revealed highly expressed MTDH and MDA-MB-231 cells had the lowest expression of MTDH. After MTDH gene was knocked down, the cell proliferation was inhibited, and the inhibitory rate of cell growth and apoptosis rate were enhanced, and the cell cycle arrest during the G0/G1 phase in the presence of doxorubicin treatment. On the other hand, the opposite results were observed in MDA-MB-231 cells with overexpressed MTDH gene.
  
  
  CONCLUSIONS
  MTDH gene plays a promoting role in the proliferation of breast cancer cells and its high expression may be associated with doxorubicin sensitivity of breast cancer.
authors.affiliation: Department of Breast Center, Fourth Hospital of Hebei Medical University No. 169 Tian Shan Street, Shijiazhuang, 050035, China.
authors.forename: Zhenchuan
authors.initials: Z
authors.lastname: Song
authors.affiliation: Department of Breast Center, Fourth Hospital of Hebei Medical University No. 169 Tian Shan Street, Shijiazhuang, 050035, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Breast Center, Fourth Hospital of Hebei Medical University No. 169 Tian Shan Street, Shijiazhuang, 050035, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Breast Center, Fourth Hospital of Hebei Medical University No. 169 Tian Shan Street, Shijiazhuang, 050035, China.
authors.forename: Donghong
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Breast Center, Fourth Hospital of Hebei Medical University No. 169 Tian Shan Street, Shijiazhuang, 050035, China.
authors.forename: Xinle
authors.initials: X
authors.lastname: Wang
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000627:therapeutic use*; D055785:Gene Knockdown Techniques; D006801:Humans; D008565:Membrane Proteins; D016601:RNA-Binding Proteins
chemical_list: D000903:Antibiotics, Antineoplastic; D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; D004317:Doxorubicin