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.

引用

页数：12

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