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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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Abstract

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.

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Acknowledgments

T. J. is a Marie Curie Fellow supported by grants MTKD-CT-2004-509836 “MACROGENEX” and MRTN-CT-2004-504228 “TAF-Chromatin” to A. P.

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Authors and Affiliations

  1. Laboratory of Signal Mediated Gene Expression, Institute of Biological Research and Biotechnology National Hellenic Research Foundation, 48 Vas Constantinou Avenue, 116 35, Athens, Greece

    Tobias Joyce & Alexander Pintzas

  2. Laboratory of Functional Genomics, The Oncogenomics Center, Institute for Cancer Research and Treatment, University of Torino, School of Medicine, 10060, Candiolo, Italy

    Daniela Cantarella, Claudio Isella & Enzo Medico

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  1. Tobias Joyce
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  2. Daniela Cantarella
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  3. Claudio Isella
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Correspondence to Alexander Pintzas.

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Joyce, T., Cantarella, D., Isella, C. et al. A molecular signature for Epithelial to Mesenchymal transition in a human colon cancer cell system is revealed by large-scale microarray analysis. Clin Exp Metastasis 26, 569–587 (2009). https://doi.org/10.1007/s10585-009-9256-9

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