HER2 Heterogeneity Is Associated with Poor Survival in HER2-Positive Breast Cancer

被引：30
|
作者：
Hosonaga, Mari [1 ]
Arima, Yoshimi [2 ]
Sampetrean, Oltea [2 ]
Komura, Daisuke [3 ]
Koya, Ikuko [4 ]
Sasaki, Takashi [5 ]
Sato, Eiichi [6 ]
Okano, Hideyuki [4 ]
Kudoh, Jun [7 ]
Ishikawa, Shumpei [3 ]
Saya, Hideyuki [2 ]
Ishikawa, Takashi [1 ]
机构：
[1] Tokyo Med Univ, Dept Breast Surg & Oncol, Shinjuku Ku, 6-7-1 Nishishinjuku, Tokyo 1600023, Japan
[2] Keio Univ, Inst Adv Med Res, Div Gene Regulat, Sch Med,Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan
[3] Tokyo Med & Dent Univ, Med Res Inst, Dept Genom Pathol, Bunkyo Ku, 1-5-45 Yushima, Tokyo 1138510, Japan
[4] Keio Univ, Dept Physiol, Sch Med, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan
[5] Keio Univ, Ctr Supercentenarian Med Res, Sch Med, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan
[6] Tokyo Med Univ, Inst Med Sci, Dept Pathol, Med Res Ctr,Shinjuku Ku, 6-7-1 Nishishinjuku, Tokyo 1600023, Japan
[7] Keio Univ, Lab Gene Med, Sch Med, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan
来源：
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2018年 / 19卷 / 08期
关键词：
HER2; heterogeneity; breast cancer; poor prognosis; caspase-1; GENE AMPLIFICATION; INTRATUMORAL HETEROGENEITY; CELLS; CARCINOMAS; EXPRESSION; CASPASE-1; EVOLUTION; IMPACT;
D O I：
10.3390/ijms19082158
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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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页数：12
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