title: NOTCH4 is a potential therapeutic target for triple-negative breast cancer.
abstract: OBJECTIVE
  The prognosis for triple-negative breast cancer (TNBC) is poor. In the present study, we evaluated whether NOTCH4 receptor is a potential new therapeutic target for TNBC.
  
  
  METHODS
  In vitro proliferation and invasiveness were evaluated in TNBC cells with or without small-interfering RNA (siRNA) for NOTCH4, and with or without NOTCH4 plasmid transfection. In vivo, MDA-MB-231 cells with or without NOTCH4 siRNA were subcutaneously implanted into the flank regions of mice. The frequency of nuclear translocation of NOTCH4 was assessed by immunohistochemistry in 21 TNBC samples and 46 non-TNBC samples.
  
  
  RESULTS
  NOTCH4 inhibition in TNBC cells reduced proliferation and invasiveness, and NOTCH4 overexpression in TNBC cells increased proliferation and invasiveness. NOTCH4 inhibition reduced tumour volume and tumourigenicity of mouse xenografts. TNBC cells had a higher frequency of nuclear translocation of NOTCH4 than other cells.
  
  
  CONCLUSIONS
  NOTCH4 is a new potential therapeutic target for triple-negative breast cancer.
authors.affiliation: Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. ohnishi@surg1.med.kyushu-u.ac.jp.
authors.forename: Iori
authors.initials: I
authors.lastname: Nagamatsu
authors.forename: Hideya
authors.initials: H
authors.lastname: Onishi
authors.forename: Shojiro
authors.initials: S
authors.lastname: Matsushita
authors.forename: Makoto
authors.initials: M
authors.lastname: Kubo
authors.forename: Masaya
authors.initials: M
authors.lastname: Kai
authors.forename: Akira
authors.initials: A
authors.lastname: Imaizumi
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakano
authors.forename: Masami
authors.initials: M
authors.lastname: Hattori
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Katano
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D016513:Mice, SCID; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D000074562:Receptor, Notch4; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: C106075:NOTCH4 protein, human; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000074562:Receptor, Notch4; D051880:Receptors, Notch
keywords: NOTCH4; Triple-negative breast cancer; breast cancer; invasion; proliferation; therapeutic target