title: TYRO3 as a potential therapeutic target in breast cancer.
abstract: OBJECTIVE
  We evaluated the potential of TYRO3 as a therapeutic target in various types of breast cancer cell lines.
  
  
  METHODS
  The effects of TYRO3-knockdown by small interfering RNA (siRNA) on proliferation, cell-cycle distribution, and cell signaling in four estrogen receptor (ER)-positive/HER2-non-amplified (luminal-type), two ER-negative/HER2-amplified (HER2-type), and two ER-negative/HER2-non-amplified (triple negative [TN]-type) cell lines were compared.
  
  
  RESULTS
  Whereas TYRO3 knockdown induced the greatest proliferation suppression in luminal-type cells, and to a lesser extent in HER2-type cells, no proliferation inhibition was observed in TN-type cells. The TYRO3 siRNA-induced proliferation inhibition in luminal-type cells was observed in both estradiol (E2)-rich and -null conditions. The proliferation suppression was correlated with G0-G1/S cell-cycle arrest. Western blot analysis showed a decrease in phosphorylation of ERK1/2 or STAT3, and in cyclin D1 only in cell lines sensitive to TYRO3-knockdown.
  
  
  CONCLUSIONS
  TYRO3 is a potential therapeutic target in breast cancer, particularly in luminal-type cells.
authors: Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors: Roudy Chiminch
authors: RC
authors: Ekyalongo
authors: Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan Cancer Center, Kobe University Hospital, Kobe, Japan mukohara@med.kobe-u.ac.jp.
authors: Toru
authors: T
authors: Mukohara
authors: Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors: Yohei
authors: Y
authors: Funakoshi
authors: Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors: Hideo
authors: H
authors: Tomioka
authors: Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors: Yu
authors: Y
authors: Kataoka
authors: Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan Division of Molecular and Cellular Biology, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors: Yohei
authors: Y
authors: Shimono
authors: Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors: Naoko
authors: N
authors: Chayahara
authors: Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors: Masanori
authors: M
authors: Toyoda
authors: Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors: Naomi
authors: N
authors: Kiyota
authors: Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan Cancer Center, Kobe University Hospital, Kobe, Japan.
authors: Hironobu
authors: H
authors: Minami
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D002453:Cell Cycle / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D061986:MCF-7 Cells; D058990:Molecular Targeted Therapy; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D064726:Triple Negative Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000628:therapy
chemical_list: D034741:RNA, Small Interfering; D020794:Receptor Protein-Tyrosine Kinases; C084944:TYRO3 protein, human
keywords: Breast cancer; TYRO3; luminal-type; siRNA; targeted therapy