Characterization and genetic analysis in the newly established human bile duct cancer cell lines.

Characterization and genetic analysis in the newly established human bile duct cancer cell lines.
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DOI:
10.3892/ijo.26.2.449
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发表时间:
2005-02
影响因子:
5.2
通讯作者:
M. Ghosh;N. Koike;S. Tsunoda;T. Hirano;S. Kaul;H. Kashiwagi;T. Kawamoto;N. Ohkohchi;K. Saijo;T. Ohno;M. Miwa;T. Todoroki
M. Ghosh;N. Koike;S. Tsunoda;T. Hirano;S. Kaul;H. Kashiwagi;T. Kawamoto;N. Ohkohchi;K. Saijo;T. Ohno;M. Miwa;T. Todoroki
中科院分区:
医学2区
文献类型:
--
作者:
M. Ghosh;N. Koike;S. Tsunoda;T. Hirano;S. Kaul;H. Kashiwagi;T. Kawamoto;N. Ohkohchi;K. Saijo;T. Ohno;M. Miwa;T. Todoroki

文献摘要

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胆管癌患者一般预后较差。以与临床管理相关的方式在生物学、遗传、分子和细胞水平上了解这种癌症对于制定有效的预防和治疗方案至关重要。然而,目前建立的胆管癌细胞系仍然不足以进行进一步了解所需的研究。本研究的目的是建立并表征人胆管癌细胞系。我们通过流式细胞术检查了所建立的细胞系的生长特征和集落形成能力,包括细胞周期参数以及肿瘤标志物(CEA、CA19-9、MUC-1和c-kit)和癌基因(c-erbB2)的表达。进行比较基因组杂交(CGH)以检测基因拷贝数的变化。通过染色体分析证实了细胞系的人类起源。我们建立了3个细胞系,并将其命名为TGBC-47、TGBC-51和TBCN-6,这三个细胞系的群体倍增时间分别为28、38和94小时。细胞保持了原始肿瘤的分化特征。两种细胞系在集落形成测定中形成集落;所有三种细胞系均表达 CEA、CA19-9、MUC-1 和 c-erbB2,并显示染色体非整倍性。 CGH 分析表明,两个细胞系中各个染色体区域均有所增加,包括 1q、5p、6p、7q 和 8q,以及三个细胞系中 17p 的缺失。这些新建立的细胞系可能作为研究胆管癌先进分子肿瘤生物学的有用模型。此外,它们可以协助转化研究开发新的有效分子靶向放化疗方案。这些染色体畸变和不平衡为参与胆管癌发生的基因组区域和基因的分子分析提供了一些起点。
Bile duct carcinoma patients generally have a poor prognosis. Understanding this cancer at the biological, genetic, molecular, and cellular level in ways relevant to clinical management is essential for developing effective preventive and therapeutic regimens. However, the currently established bile duct cancer cell lines are still insufficient for the research required to attain such an improved understanding. The aim of this study was to establish and characterize human bile duct cancer cell lines. We examined the growth characteristics and colony-forming ability of the established cell lines in terms of their cell cycle parameters and expression of tumor markers (CEA, CA19-9, MUC-1 and c-kit) and oncogene (c-erbB2) by flow cytometry. Comparative genomic hybridization (CGH) was performed to detect changes in the gene copy numbers. Human origin of the cell lines was confirmed by chromosomal analysis. We have established 3 cell lines and designated them as TGBC-47, TGBC-51, and TBCN-6 and the population doubling times of the three cell lines were 28, 38 and 94 h, respectively. The cells maintained differentiation characteristics of the original tumors. Two cell lines formed colonies in the colony forming assays; all three-cell lines expressed CEA, CA19-9, MUC-1 and c-erbB2 and showed chromosomal aneuploidy. CGH analysis demonstrated gains in various chromosomal regions, including 1q, 5p, 6p, 7q and 8q in two cell lines, and the loss in 17p in three cell lines. These newly established cell lines might serve as useful models for studying the advanced molecular tumor biology of bile duct cancer. Furthermore, they may assist translational research in the development of new effective molecular targeting chemoradiotherapy regimens. These chromosomal aberrations and imbalances provide some starting points for the molecular analysis of genomic regions and genes involved in bile duct carcinogenesis.