NOTCH4 is a potential therapeutic target for triple-negative breast cancer

Iori Nagamatsu, Hideya Onishi, Shojiro Matsushita, Makoto Kubo, Masaya Kai, Akira Imaizumi, Kenji Nakano, Masami Hattori, Yoshinao Oda, Masao Tanaka, Mitsuo Katano

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

Abstract

Background/Aim: 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. Materials and 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. Conclusion: NOTCH4 is a new potential therapeutic target for triple-negative breast cancer.

Original languageEnglish
Pages (from-to)69-80
Number of pages12
JournalAnticancer research
Volume34
Issue number1
Publication statusPublished - Jan 1 2014

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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