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源自中国乳腺癌且在TP53 DNA结合结构域具有相同错义突变的三种稳定的基底样/HER2阳性乳腺癌细胞系的建立与鉴定

Establishment and characterization of three stable Basal/HER2-positive breast cancer cell lines derived from Chinese breast carcinoma with identical missense mutations in the DNA-binding domain of TP53.

作者信息

Zhou Fei, Zhang Yanhua, Xu Xiufang, Luo Jingfeng, Yang Fang, Wang Linbo, Xie Shuduo, Sun Jihong, Yang Xiaoming

机构信息

1Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang China.

2Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang China.

出版信息

Cancer Cell Int. 2018 Aug 17;18:118. doi: 10.1186/s12935-018-0617-9. eCollection 2018.

Abstract

BACKGROUND

Basal/human epidermal growth factor receptor (HER)2-positive (HER2+) breast cancer is resistant to monoclonal antibody (herceptin) treatment. There are currently only three basal/HER2+ breast cancer cell lines available, but they are not from Chinese populations.

METHODS

Three immortalized cell lines (ZJU-0327, ZJU-0725, and ZJU-1127) were established from invasive ductal breast carcinoma tissue of two patients treated by surgical resection at our center. The cell lines were characterized in terms of histology, therapeutic response, and biomarker expression. Their tumorigenic potential was evaluated in an athymic nude (BALB/C nu) mouse xenograft model. Cell authentication testing by the techniques of short tandem repeat.

RESULTS

ZJU-0327, ZJU-0725, and ZJU-1127 cell lines were maintained for more than 110 passages in vitro. The cells grew as monolayers; showed typical epithelial morphology and ultrastructure; were polyploid; had doubling times of 18, 57.5, and 18 h, respectively; had a near-tetraploid (ZJU-0327 and ZJU-1127) or aneuploid (ZJU-0725) karyotype with structural aberrations and tumor protein 53 mutation; insensitive to chemotherapeutic drugs and/or radiation; show high invasiveness and tumorigenicity in mice; and had no mycoplasma contamination. The cell lines were basal/HER2+, expressed cluster of differentiation, and were associated with poor prognosis. Cell authentication testing by the American Type Culture Collection confirmed the human origin of the cell lines, which did not match those in existing databases.

CONCLUSIONS

The three novel basal/HER2+ breast cancer cell lines recapitulating the malignant characteristics of the parent tumor's, and can be useful for clarifying the molecular pathogenesis of basal/HER2+ breast cancer.

摘要

背景

基底样/人表皮生长因子受体2阳性(HER2+)乳腺癌对单克隆抗体(赫赛汀)治疗耐药。目前仅有三种基底样/HER2+乳腺癌细胞系可用,但它们并非来自中国人群。

方法

从我们中心接受手术切除治疗的两名患者的浸润性导管癌组织中建立了三种永生化细胞系(ZJU - 0327、ZJU - 0725和ZJU - 1127)。对这些细胞系进行了组织学、治疗反应和生物标志物表达方面的表征。在无胸腺裸(BALB/C nu)小鼠异种移植模型中评估了它们的致瘤潜力。通过短串联重复序列技术进行细胞鉴定测试。

结果

ZJU - 0327、ZJU - 0725和ZJU - 1127细胞系在体外传代超过110次。细胞呈单层生长;表现出典型的上皮形态和超微结构;为多倍体;倍增时间分别为18、57.5和18小时;具有近四倍体(ZJU - 0327和ZJU - 1127)或非整倍体(ZJU - 0725)核型,伴有结构畸变和肿瘤蛋白53突变;对化疗药物和/或辐射不敏感;在小鼠中表现出高侵袭性和致瘤性;且无支原体污染。这些细胞系为基底样/HER2+,表达分化簇,且与预后不良相关。美国典型培养物保藏中心的细胞鉴定测试证实了这些细胞系的人源性质,它们与现有数据库中的细胞系不匹配。

结论

这三种新型基底样/HER2+乳腺癌细胞系概括了亲本肿瘤的恶性特征,可用于阐明基底样/HER2+乳腺癌的分子发病机制。

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