Ertel Adam, Verghese Arun, Byers Stephen W, Ochs Michael, Tozeren Aydin
Center for Integrated Bioinformatics, School of Biomedical Engineering, Science and Health Systems, Bossone 714, Drexel University, 3143 Chestnut Street, Philadelphia, PA 19104, USA.
Mol Cancer. 2006 Nov 2;5(1):55. doi: 10.1186/1476-4598-5-55.
Cell lines are used in experimental investigation of cancer but their capacity to represent tumor cells has yet to be quantified. The aim of the study was to identify significant alterations in pathway usage in cell lines in comparison with normal and tumor tissue.
This study utilized a pathway-specific enrichment analysis of publicly accessible microarray data and quantified the gene expression differences between cell lines, tumor, and normal tissue cells for six different tissue types. KEGG pathways that are significantly different between cell lines and tumors, cell lines and normal tissues and tumor and normal tissue were identified through enrichment tests on gene lists obtained using Significance Analysis of Microarrays (SAM).
Cellular pathways that were significantly upregulated in cell lines compared to tumor cells and normal cells of the same tissue type included ATP synthesis, cell communication, cell cycle, oxidative phosphorylation, purine, pyrimidine and pyruvate metabolism, and proteasome. Results on metabolic pathways suggested an increase in the velocity nucleotide metabolism and RNA production. Pathways that were downregulated in cell lines compared to tumor and normal tissue included cell communication, cell adhesion molecules (CAMs), and ECM-receptor interaction. Only a fraction of the significantly altered genes in tumor-to-normal comparison had similar expressions in cancer cell lines and tumor cells. These genes were tissue-specific and were distributed sparsely among multiple pathways.
Significantly altered genes in tumors compared to normal tissue were largely tissue specific. Among these genes downregulation was a major trend. In contrast, cell lines contained large sets of significantly upregulated genes that were common to multiple tissue types. Pathway upregulation in cell lines was most pronounced over metabolic pathways including cell nucleotide metabolism and oxidative phosphorylation. Signaling pathways involved in adhesion and communication of cultured cancer cells were downregulated. The three way pathways comparison presented in this study brings light into the differences in the use of cellular pathways by tumor cells and cancer cell lines.
细胞系被用于癌症的实验研究，但其代表肿瘤细胞的能力尚未得到量化。本研究的目的是确定与正常组织和肿瘤组织相比，细胞系中信号通路使用情况的显著变化。
本研究利用对公开可用的微阵列数据进行特定信号通路富集分析，并对六种不同组织类型的细胞系、肿瘤组织和正常组织细胞之间的基因表达差异进行量化。通过对使用微阵列显著性分析（SAM）获得的基因列表进行富集测试，确定细胞系与肿瘤、细胞系与正常组织以及肿瘤与正常组织之间显著不同的KEGG信号通路。
与相同组织类型的肿瘤细胞和正常细胞相比，细胞系中显著上调的细胞信号通路包括ATP合成、细胞通讯、细胞周期、氧化磷酸化、嘌呤、嘧啶和丙酮酸代谢以及蛋白酶体。代谢信号通路的结果表明核苷酸代谢速度和RNA产生增加。与肿瘤组织和正常组织相比，细胞系中下调的信号通路包括细胞通讯、细胞粘附分子（CAMs）和细胞外基质受体相互作用。在肿瘤与正常组织比较中显著改变的基因中，只有一小部分在癌细胞系和肿瘤细胞中具有相似的表达。这些基因是组织特异性的，并且稀疏地分布在多个信号通路中。
与正常组织相比，肿瘤中显著改变的基因在很大程度上是组织特异性的。在这些基因中，下调是主要趋势。相比之下，细胞系包含大量多种组织类型共有的显著上调基因。细胞系中信号通路的上调在包括细胞核苷酸代谢和氧化磷酸化在内的代谢信号通路上最为明显。参与培养癌细胞粘附和通讯的信号通路被下调。本研究中呈现的三方信号通路比较揭示了肿瘤细胞和癌细胞系在细胞信号通路使用上的差异。
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