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 Kudoh; Shumpei Ishikawa; Hideyuki Saya; Takashi Ishikawa

doi:10.3390/ijms19082158

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 Kudoh, Shumpei Ishikawa, Hideyuki Saya, Takashi Ishikawa

Research output: Contribution to journal › Article › peer-review

24 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 language	English
Article number	2158
Journal	International journal of molecular sciences
Volume	19
Issue number	8
DOIs	https://doi.org/10.3390/ijms19082158
Publication status	Published - 2018 Aug

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/ijms19082158

Cite this

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title = "HER2 heterogeneity is associated with poor survival in HER2-positive breast cancer",

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.",

keywords = "Breast cancer, Caspase-1, HER2, Heterogeneity, Poor prognosis",

author = "Mari Hosonaga and Yoshimi Arima and Oltea Sampetrean and Daisuke Komura and Ikuko Koya and Takashi Sasaki and Eiichi Sato and Hideyuki Okano and Jun Kudoh and Shumpei Ishikawa and Hideyuki Saya and Takashi Ishikawa",

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year = "2018",

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language = "English",

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journal = "International journal of molecular sciences",

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T1 - HER2 heterogeneity is associated with poor survival in HER2-positive breast cancer

AU - Hosonaga, Mari

AU - Arima, Yoshimi

AU - Sampetrean, Oltea

AU - Komura, Daisuke

AU - Koya, Ikuko

AU - Sasaki, Takashi

AU - Sato, Eiichi

AU - Okano, Hideyuki

AU - Kudoh, Jun

AU - Ishikawa, Shumpei

AU - Saya, Hideyuki

AU - Ishikawa, Takashi

PY - 2018/8

Y1 - 2018/8

N2 - 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.

AB - 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.

KW - Breast cancer

KW - Caspase-1

KW - HER2

KW - Heterogeneity

KW - Poor prognosis

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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