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

• Published in: International journal of molecular sciences Vol. 19; no. 8; p. 2158
• Main Authors: Hosonaga, Mari, Arima, Yoshimi, Sampetrean, Oltea, Komura, Daisuke, Koya, Ikuko, Sasaki, Takashi, Sato, Eiichi, Okano, Hideyuki, Kudoh, Jun, Ishikawa, Shumpei, Saya, Hideyuki, Ishikawa, Takashi
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24.07.2018; MDPI
• Subjects: Animal models; Biological effects; Brain tumors; Breast cancer; Caspase; Caspase-1; Communication; Epidermal growth factor; ErbB-2 protein; Growth factors; HER2; Heterogeneity; Lesions; Metastases; Metastasis; Nucleotide sequence; poor prognosis; Survival; poor prognosis; breast cancer; HER2; caspase-1; heterogeneity
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19082158

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 ( = 24), 24 ( = 22) and 30 ( = 13) days, respectively. RNA sequence analysis showed that 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.