A molecular signature for Epithelial to Mesenchymal transition in a human colon cancer cell system is revealed by large-scale microarray analysis
A molecular signature for Epithelial to Mesenchymal transition in a human colon cancer cell system is revealed by large-scale microarray analysis
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DOI：
10.1007/s10585-009-9256-9
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发表时间：
2009-08-01
影响因子：
4
通讯作者：
Pintzas, Alexander
中科院分区：
文献类型：
--
作者：
Joyce, Tobias;Cantarella, Daniela;Pintzas, Alexander
散发性结直肠癌是世界范围内的一个主要死亡原因。从良性腺瘤到癌的发展是循序渐进的。在90%携带Ras突变的肿瘤中，Ki-Ras发生了突变。我们开发了一种模型细胞系统来研究结直肠癌细胞系中的致癌Ras突变。在本分析中，两个分别表达Ha-RasV12 （Caco-H）和Ki-RasV12 （Caco-K）的Caco-2衍生细胞系被用于大规模微阵列分析，以对照Caco-2。这是使用包含24,000个基因的Illumina微阵列进行的。基因已被确定为在每个异构体中差异表达以及共同调节。此外，Caco-H细胞系具有很强的上皮间充质表型，这反映在其许多差异表达的基因上。这些包括已知的EMT标记物Vimentin， E-cadherin和Slug。其他感兴趣的基因包括Claudin家族的几个成员，Forkhead转录因子和gata因子。Caco-K细胞系显示Dickkopf转录抑制因子的强烈下调，暗示其参与WNT信号传导。使用Ingenuity软件对两种细胞系的差异表达基因进行了途径和功能分析。这种全基因组微阵列分析为Caco-H结肠癌细胞系的EMT提供了分子特征。它还揭示了Caco-K表达的一些关键基因，并鉴定了Ras表达的新标记，这些标记已通过PCR分析得到验证。
Sporadic colorectal cancer is a major cause of death worldwide. Development takes place in a sequential manner from benign adenomas leading to carcinomas. In 90% of tumours bearing a Ras mutation it is Ki-Ras that is mutated. We have developed a model cell system to study oncogenic Ras mutations in colorectal cancer cell lines. In this analysis two Caco-2 derived cell lines expressing Ha-RasV12 (Caco-H) and Ki-RasV12 (Caco-K), respectively, have been used in large-scale microarray profiling against a Caco-2 control. This was carried out using an Illumina microarray containing 24,000 genes. Genes have been identified as differentially expressed in each isoform as well as commonly regulated. In addition the Caco-H cell line has a strong epithelial-mesenchymal phenotype that is reflected in many of its differentially expressed genes. These include the known EMT markers Vimentin, E-cadherin and Slug. Other genes of interest include several members of the Claudin family, Forkhead transcription factors and GATA-factors. The Caco-K cell line shows strong downregulation of the Dickkopf transcriptional repressor implicating it in WNT signalling. Pathway and functional analysis has also been carried out for the differentially expressed genes for both cell lines using Ingenuity software. This genome wide microarray analysis has provided a molecular signature for EMT in a Caco-H colon cancer cell line. It has also revealed a number of key genes for Caco-K expression and identified novel markers for Ras expression that have been verified by PCR analysis.