TY - JOUR
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
N1 - Funding Information:
Funding: This work was supported by KAKENHI grants 25461995 and 16K10473 to Y.A., and a Grant-in-Aid for Scientific Research on Innovative Areas “Development of Novel Treatment Strategies Targeting Cancer Stem Cells” 22130007 to H.S. from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan.
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.
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U2 - 10.3390/ijms19082158
DO - 10.3390/ijms19082158
M3 - Article
C2 - 30042341
AN - SCOPUS:85051995550
VL - 19
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 8
M1 - 2158
ER -