title: Midostaurin preferentially attenuates proliferation of triple-negative breast cancer cell lines through inhibition of Aurora kinase family.
abstract: BACKGROUND
  Breast cancer is classified into three subtypes by the expression of biomarker receptors such as hormone receptors and human epidermal growth factor receptor 2. Triple-negative breast cancer (TNBC) expresses none of these receptors and has an aggressive phenotype with a poor prognosis, which is insensitive to the drugs that target the hormone receptors and human epidermal growth factor receptor 2. It is, thus, required to develop an effective therapeutic reagent to treat TNBC.
  
  
  RESULTS
  The study using a panel of 19 breast cancer cell lines revealed that midostaurin, a multi-target protein kinase inhibitor, suppresses preferentially the growth of TNBC cells comparing with non-TNBC cells. Clustering analysis of the drug activity data for the panel of cancer cell lines predicted that midostaurin shares the target with Aurora kinase inhibitors. Following studies indicated that midostaurin attenuates the phosphorylation reaction mediated by Aurora kinase in the cells and directly inhibits this protein kinase in vitro, and that this reagent induces apoptosis accompanying accumulation of 4N and 8N DNA cells in TNBC cells.
  
  
  CONCLUSIONS
  Midostaurin suppresses the proliferation of TNBC cells among the breast cancer cell lines presumably through the inhibition of the Aurora kinase family. The precise study of midostaurin on cell growth will contribute to the development of the drug for the treatment of TNBC.
authors.affiliation: Biosignal Research Center, Kobe University, Kobe, 657-8501, Japan. 090s381s@stu.kobe-u.ac.jp.|Department of Biology, Graduate School of Science, Kobe University, Kobe, 657-8501, Japan. 090s381s@stu.kobe-u.ac.jp.|Central Research Laboratories, Sysmex Corporation, Kobe, 651-2271, Japan. 090s381s@stu.kobe-u.ac.jp.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kawai
authors.affiliation: Biosignal Research Center, Kobe University, Kobe, 657-8501, Japan. anakashima@person.kobe-u.ac.jp.
authors.forename: Akio
authors.initials: A
authors.lastname: Nakashima
authors.affiliation: Biosignal Research Center, Kobe University, Kobe, 657-8501, Japan. skamada@kobe-u.ac.jp.|Department of Biology, Graduate School of Science, Kobe University, Kobe, 657-8501, Japan. skamada@kobe-u.ac.jp.|Present Address: Research Center for Environmental Genomics, Kobe University, Kobe, 657-8501, Japan. skamada@kobe-u.ac.jp.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kamada
authors.affiliation: Biosignal Research Center, Kobe University, Kobe, 657-8501, Japan. ukikkawa@kobe-u.ac.jp.|Department of Bioresource Science, Graduate School of Agricultural Science, Kobe University, Kobe, 657-8501, Japan. ukikkawa@kobe-u.ac.jp.
authors.forename: Ushio
authors.initials: U
authors.lastname: Kikkawa
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D064096:Aurora Kinase A / Q000096:biosynthesis* / Q000235:genetics; D064107:Aurora Kinase B / Q000096:biosynthesis* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D019311:Staurosporine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D047428:Protein Kinase Inhibitors; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D019311:Staurosporine; C059539:midostaurin