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自发永生化建立并鉴定的两个人乳腺癌细胞系:乳腺癌组织中雌激素、孕激素和 HER2/neu 受体与衍生细胞系之间的不匹配。

Establishment and characterization of two human breast carcinoma cell lines by spontaneous immortalization: Discordance between Estrogen, Progesterone and HER2/neu receptors of breast carcinoma tissues with derived cell lines.

机构信息

Genetic Medicine Research Centre, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia UPM Serdang, Selangor, 43400, Malaysia.

出版信息

Cancer Cell Int. 2012 Oct 29;12(1):43. doi: 10.1186/1475-2867-12-43.

Abstract

BACKGROUND

Breast cancer is one of the most common cancers among women throughout the world. Therefore, established cell lines are widely used as in vitro experimental models in cancer research.

METHODS

Two continuous human breast cell lines, designated MBC1 and MBC2, were successfully established and characterized from invasive ductal breast carcinoma tissues of Malaysian patients. MBC1 and MBC2 have been characterized in terms of morphology analysis, population doubling time, clonogenic formation, wound healing assay, invasion assay, cell cycle, DNA profiling, fluorescence immunocytochemistry, Western blotting and karyotyping.

RESULTS

MBC1 and MBC2 exhibited adherent monolayer epithelial morphology at a passage number of 150. Receptor status of MBC1 and MBC2 show (ER+, PR+, HER2+) and (ER+, PR-, HER2+), respectively. These results are in discordance with histopathological studies of the tumoral tissues, which were triple negative and (ER-, PR-, HER2+) for MBC1 and MBC2, respectively. Both cell lines were capable of growing in soft agar culture, which suggests their metastatic potential. The MBC1 and MBC2 metaphase spreads showed an abnormal karyotype, including hyperdiploidy and complex rearrangements with modes of 52-58 chromosomes per cell.

CONCLUSIONS

Loss or gain in secondary properties, deregulation and specific genetic changes possibly conferred receptor changes during the culturing of tumoral cells. Thus, we hypothesize that, among heterogenous tumoral cells, only a small minority of ER+/PR+/HER2+ and ER+/PR-/HER2+ cells with lower energy metabolism might survive and adjust easily to in vitro conditions. These cell lines will pave the way for new perspectives in genetic and biological investigations, drug resistance and chemotherapy studies, and would serve as prototype models in Malaysian breast carcinogenesis investigations.

摘要

背景

乳腺癌是全世界女性最常见的癌症之一。因此,已建立的细胞系被广泛用作癌症研究中的体外实验模型。

方法

从马来西亚患者的浸润性导管乳腺癌组织中成功建立并鉴定了两个连续的人乳腺细胞系,分别命名为 MBC1 和 MBC2。MBC1 和 MBC2 的特征在于形态分析、倍增时间、集落形成、划痕愈合试验、侵袭试验、细胞周期、DNA 图谱分析、荧光免疫细胞化学、Western 印迹和核型分析。

结果

MBC1 和 MBC2 在传代 150 次时表现出贴壁单层上皮形态。MBC1 和 MBC2 的受体状态分别为(ER+、PR+、HER2+)和(ER+、PR-、HER2+)。这些结果与肿瘤组织的组织病理学研究不一致,MBC1 和 MBC2 分别为三阴性和(ER-、PR-、HER2+)。两种细胞系均能够在软琼脂培养中生长,这表明它们具有转移潜能。MBC1 和 MBC2 的中期分裂象显示出异常的核型,包括超二倍体和复杂重排,每个细胞的模式为 52-58 条染色体。

结论

在肿瘤细胞培养过程中,次级特性的丧失或获得、失调和特定的遗传变化可能导致受体发生变化。因此,我们假设,在异质性肿瘤细胞中,只有少数 ER+/PR+/HER2+和 ER+/PR-/HER2+细胞具有较低的能量代谢,可能存活并容易适应体外条件。这些细胞系将为遗传和生物学研究、耐药性和化疗研究以及马来西亚乳腺癌发生研究中的原型模型开辟新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dd2/3527183/87e159a15bf8/1475-2867-12-43-1.jpg

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