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

Alexander Baras, Y. Yu, M. Filtz, B. Kim, C. A. Moskaluk

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2919-2924
Number of pages6
JournalOncogene
Volume28
Issue number32
DOIs
StatePublished - Aug 13 2009
Externally publishedYes

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Gene Expression Profiling
Squamous Cell Carcinoma
DNA
Genes
Proteins
Gene Expression
Gene Amplification
Cyclin D1
Epidermal Growth Factor Receptor
Small Interfering RNA
Esophagus
Tobacco
Single Nucleotide Polymorphism
Real-Time Polymerase Chain Reaction
Mucous Membrane
Cell Death
Cell Line
Lung

Keywords

  • ECOP
  • EGFR
  • Microarray
  • Squamous cell carcinoma
  • Tobacco

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Combined genomic and gene expression microarray profiling identifies ECOP as an upregulated gene in squamous cell carcinomas independent of DNA amplification. / Baras, Alexander; Yu, Y.; Filtz, M.; Kim, B.; Moskaluk, C. A.

In: Oncogene, Vol. 28, No. 32, 13.08.2009, p. 2919-2924.

Research output: Contribution to journalArticle

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