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头颈部鳞状细胞癌细胞系的细胞遗传学特征作为肿瘤相关基因功能分析的模型系统。

Cytogenetic characterization of head and neck squamous cell carcinoma cell lines as model systems for the functional analyses of tumor-associated genes.

机构信息

Abteilung Molekulare Genetik (B060), Deutsches Krebsforschungszentrum, Heidelberg, Germany.

出版信息

J Oral Pathol Med. 2010 May;39(5):382-9. doi: 10.1111/j.1600-0714.2009.00864.x. Epub 2010 Feb 8.

DOI:10.1111/j.1600-0714.2009.00864.x
PMID:20149059
Abstract

Head and neck squamous cell carcinoma (HNSCC) is a solid malignant neoplasm exhibiting aggressive phenotypes and high recurrence rates. To improve its clinical management, understanding the molecular basis of HNSCC development is of critical importance. For the investigation of tumor-associated genes, functional analyses in well-characterized tumor cell systems are required. To establish an experimental platform, a set of 20 HNSCC cell lines was screened for genetic imbalances by chromosomal comparative genomic hybridization (cCGH). Frequent DNA copy number gains were detected on 3q26.3-qter, 5p, 7p11-p13, 8q23-qter, 9p11-p13, 9q31-qter, 11q13 and 20q13.1, whereas copy number losses were found on 3p, 4p, 4q32.1-qter, 8p11-p12 and 18q22 in agreement with previous observations on genetic aberrations detected in primary HNSCC specimens. Subsequent mRNA expression analysis of 11q13 candidate genes CCND1 and CTTN revealed that HNSCC cell lines exhibiting a DNA copy number gain on 11q13 had a higher transcript level of CCND1 and CTTN compared with HNSCC cell lines without 11q13 copy number gain (P = 0.014 and P = 0.009, respectively). Furthermore, CCND1 and CTTN amplification as detected by fluorescence in situ hybridization correlated with protein expression as assessed by immunocytochemistry. In summary, the cytogenetic characterization illustrates that this set of HNSCC cell lines is representative for the HNSCC genome and provides tumor model systems for detailed analysis of genes with a possible role in the pathomechanism of head and neck tumors.

摘要

头颈部鳞状细胞癌(HNSCC)是一种表现出侵袭性表型和高复发率的实体恶性肿瘤。为了改善其临床管理,了解 HNSCC 发展的分子基础至关重要。为了研究肿瘤相关基因,需要在具有良好特征的肿瘤细胞系统中进行功能分析。为了建立一个实验平台,通过染色体比较基因组杂交(cCGH)筛选了一组 20 种 HNSCC 细胞系,以检测遗传失衡。在 3q26.3-qter、5p、7p11-p13、8q23-qter、9p11-p13、9q31-qter、11q13 和 20q13.1 上检测到频繁的 DNA 拷贝数增益,而在 3p、4p、4q32.1-qter、8p11-p12 和 18q22 上检测到拷贝数丢失,这与先前在原发性 HNSCC 标本中检测到的遗传异常一致。随后对 11q13 候选基因 CCND1 和 CTTN 的 mRNA 表达分析表明,与没有 11q13 拷贝数增益的 HNSCC 细胞系相比,在 11q13 上具有 DNA 拷贝数增益的 HNSCC 细胞系中 CCND1 和 CTTN 的转录水平更高(P = 0.014 和 P = 0.009)。此外,荧光原位杂交检测到的 CCND1 和 CTTN 扩增与免疫细胞化学评估的蛋白质表达相关。总之,细胞遗传学特征表明,这组 HNSCC 细胞系代表了 HNSCC 基因组,并为详细分析可能在头颈部肿瘤发病机制中起作用的基因提供了肿瘤模型系统。

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