HER2 heterogeneity is associated with poor survival in HER2-positive breast cancer

Mari Hosonaga, Yoshimi Arima, Oltea Sampetrean, Daisuke Komura, Ikuko Koya, Takashi Sasaki, Eiichi Sato, Hideyuki Okano, Jun Kudo, Shumpei Ishikawa, Hideyuki Saya, Takashi Ishikawa

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4 Citations (Scopus)

Abstract

Intratumoral human epidermal growth factor receptor 2 (HER2) heterogeneity has been reported in 16–36% of HER2-positive breast cancer and its clinical impact is under discussion. We examined the biological effects of HER2-heterogeneity on mouse models and analyzed metastatic brains by RNA sequence analysis. A metastatic mouse model was developed using 231-Luc (triple negative cells) and 2 HER2-positive cell lines, namely, HER2-60 and HER2-90 which showed heterogeneous and monotonous HER2 expressions, respectively. Metastatic lesions developed in 3 weeks in all the mice injected with HER2-60 cells, and in 69% of the mice injected with HER2-90 and 87.5% of the mice injected with 231-Luc. The median survival days of mice injected with 231-Luc, HER2-60, and HER2-90 cells were 29 (n = 24), 24 (n = 22) and 30 (n = 13) days, respectively. RNA sequence analysis showed that CASP-1 and its related genes were significantly downregulated in metastatic brain tumors with HER2-60 cells. The low expression of caspase-1 could be a new prognostic biomarker for early relapse in HER2-positive breast cancer.

Original languageEnglish
Article number2158
JournalInternational Journal of Molecular Sciences
Volume19
Issue number8
DOIs
Publication statusPublished - 2018 Aug 1

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Keywords

  • Breast cancer
  • Caspase-1
  • HER2
  • Heterogeneity
  • Poor prognosis

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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