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从台湾绝经前女性中建立具有极低致瘤性的两个基底样乳腺癌细胞系。

Establishment of two basal-like breast cancer cell lines with extremely low tumorigenicity from Taiwanese premenopausal women.

机构信息

Division of Breast Surgery and General Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Guishan Dist., Taoyuan, 33305, Taiwan.

Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, 33302, Taiwan.

出版信息

Hum Cell. 2018 Apr;31(2):154-166. doi: 10.1007/s13577-017-0197-3. Epub 2018 Feb 26.

Abstract

The research of carcinogenetic mechanisms of breast cancer in different ethnic backgrounds is an interesting field, as clinical features of breast cancers vary among races. High premenopausal incidence is distinctive in East-Asian breast cancer. However, human cell lines derived from Asian primary breast tumor are rare. To provide alternative cell line models with a relevant genetic background, we aimed to establish breast cancer cell lines from Taiwanese patients of Han-Chinese ethnicity. Fresh tissue from mammary tumors were digested into organoids, plated and grown in basal serum-free medium of human mammary epithelial cells (HuMEC) with supplements. Cells were further enriched by positive selection with CD326 (epithelial cell adhesion molecule; EpCAM)-coated micro-magnetic beads. Two breast cancer cell lines derived from premenopausal women were successfully established by this method, and named Chang-Gung Breast Cancer 01 (CGBC 01) and 02 (CGBC 02). These two cell lines had a similar phenotype with weak expression of estrogen receptor (ER), progesterone receptor (PR), and without amplification of receptor tyrosine protein kinase erbB-2 (HER2/neu). Genome-wide Single Nucleotide Polymorphism (SNP) array showed multiple copy number alterations in both cell lines. Based on gene expression profiles, CGBC 01 and 02 were clustered into basal-like subtype with reference to the breast cancer cell line gene expression database. The tumorigenicity of both cell lines was extremely low in both anchorage-independence assay and transplantation into the mammary fat pads of nude mice. CGBC 01 and CGBC 02 are low tumorigenic breast cancer cell lines, established from Han-Chinese premenopausal breast cancer patients, which serve as in vitro models in studying the biological features of Asian breast cancer.

摘要

不同种族背景下乳腺癌致癌机制的研究是一个有趣的领域,因为乳腺癌的临床特征在不同种族之间存在差异。东亚乳腺癌的绝经前发病率较高。然而,源自亚洲原发性乳腺癌的人源细胞系却很少。为了提供具有相关遗传背景的替代细胞系模型,我们旨在建立来自华裔台湾人乳腺癌患者的乳腺癌细胞系。从乳腺肿瘤的新鲜组织中消化出类器官,接种并在含有补充物的人乳腺上皮细胞(HuMEC)基础无血清培养基中生长。通过用 CD326(上皮细胞黏附分子;EpCAM)包被的微磁珠进行阳性选择,进一步富集细胞。通过这种方法成功建立了两株源自绝经前女性的乳腺癌细胞系,分别命名为长庚乳腺癌 01 号(CGBC 01)和 02 号(CGBC 02)。这两个细胞系具有相似的表型,雌激素受体(ER)、孕激素受体(PR)表达较弱,且受体酪氨酸蛋白激酶 erbB-2(HER2/neu)无扩增。全基因组单核苷酸多态性(SNP)芯片显示两个细胞系均存在多个拷贝数改变。根据基因表达谱,CGBC 01 和 02 被聚类为基底样亚型,参照乳腺癌细胞系基因表达数据库。在无锚定依赖性测定和移植到裸鼠乳腺脂肪垫中,这两个细胞系的致瘤性均极低。CGBC 01 和 CGBC 02 是源自华裔绝经前乳腺癌患者的低致瘤性乳腺癌细胞系,可作为研究亚洲乳腺癌生物学特征的体外模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fe1/5852199/0ce52cb68ae9/13577_2017_197_Fig1_HTML.jpg

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