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Combined genomic and gene expression microarray profiling identifies ECOP as an upregulated gene in squamous cell carcinomas independent of DNA amplification

Oncogene volume 28, pages 2919–2924 (2009)Cite this article

Abstract

To identify dysregulated genes that may play a role in the pathogenesis of tobacco-related human squamous cell carcinoma (SCC), a cohort of SCCs from smokers (29 SCC of the head and neck, 3 SCC of the esophagus and 46 SCC of the lungs) were concomitantly analyzed for gene expression using Affymetrix U133A 2.0 arrays and for genomic variation using Affymetrix Human Mapping 100 K set. Gene expression profiling clearly separated benign squamous mucosa (BSM) from SCC and identified several candidate genes relevant to the biology of SCC. The single-nucleotide polymorphism array data adapted for copy number analysis identified two discrete areas of high-level genomic amplification, including 7p11.2 (EGFR (epidermal growth factor receptor)) and 11q13.3 (CCND1 (cyclin D1)). When gene expression measures were correlated with amplification status at 7p11.2 locus, EGFR overexpression in relation to benign tissue was dependent on amplification and occurred in only 9% of cases. However, an adjacent gene (∼0.4 Mb), EGFR-co-amplified and overexpressed protein (ECOP), showed strong over-expression in the majority (90%) of SCCs regardless of gene amplification status. This finding was corroborated with quantitative real-time PCR assays and protein immunoblots. Interestingly, small interfering RNA-mediated knockdown of ECOP gene products in a SCC cell line (SCC-9) resulted in increased cell death. The results of these studies identify ECOP as a protein relevant to the biology of SCC.

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Acknowledgements

We wish to thank Ms Angela Miller for her support of the histological techniques required to carry out these studies. We wish to thank Dr Patcharin Pramoonjago for assistance in the creation and evaluation of antibody reagents to the ECOP protein. Alex Baras is a member of the Biotechnology Training Program at The University of Virginia, supported by training grant, T32 GM008715, from the National Institutes of Health (USA). These studies were primarily supported by a grant from the Virginia Tobacco Settlement Foundation. This project was also supported, in part, by a gift provided to the University of Virginia by Philip Morris USA. The review and approval process was overseen by an External Advisory Committee without any affiliation with the University, PM USA, or any other tobacco company. Funding for this project was based upon independent intramural and extramural reviews.

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Authors and Affiliations

  1. Department of Pathology, University of Virginia, Charlottesville, VA, USA

    A Baras, Y Yu, M Filtz, B Kim & C A Moskaluk

  2. Department of Biochemistry & Molecular Genetics, University of Virginia, Charlottesville, VA, USA

    C A Moskaluk

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  1. A Baras
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  2. Y Yu
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  3. M Filtz
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Correspondence to C A Moskaluk.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Baras, A., Yu, Y., Filtz, M. et al. Combined genomic and gene expression microarray profiling identifies ECOP as an upregulated gene in squamous cell carcinomas independent of DNA amplification. Oncogene 28, 2919–2924 (2009). https://doi.org/10.1038/onc.2009.150

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  • DOI: https://doi.org/10.1038/onc.2009.150

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