Gene Set: LI_AMPLIFIED_IN_LUNG_CANCER

Standard name LI_AMPLIFIED_IN_LUNG_CANCER
Systematic name M5792
Brief description Genes with increased copy number that correlates with increased expression across six different lung adenocarcinoma cell lines.
Full description or abstract Amplification and overexpression of putative oncogenes confer growth advantages for tumor development. We used a functional genomic approach that integrated simultaneous genomic and transcript microarray, proteomics, and tissue microarray analyses to directly identify putative oncogenes in lung adenocarcinoma. We first identified 183 genes with increases in both genomic copy number and transcript in six lung adenocarcinoma cell lines. Next, we used two-dimensional polyacrylamide gel electrophoresis and mass spectrometry to identify 42 proteins that were overexpressed in the cancer cells relative to normal cells. Comparing the 183 genes with the 42 proteins, we identified four genes - PRDX1, EEF1A2, CALR, and KCIP-1 - in which elevated protein expression correlated with both increased DNA copy number and increased transcript levels (all r > 0.84, two-sided P < 0.05). These findings were validated by Southern, Northern, and Western blotting. Specific inhibition of EEF1A2 and KCIP-1 expression with siRNA in the four cell lines tested suppressed proliferation and induced apoptosis. Parallel fluorescence in situ hybridization and immunohistochemical analyses of EEF1A2 and KCIP-1 in tissue microarrays from patients with lung adenocarcinoma showed that gene amplification was associated with high protein expression for both genes and that protein overexpression was related to tumor grade, disease stage, Ki-67 expression, and a shorter survival of patients. The amplification of EEF1A2 and KCIP-1 and the presence of overexpressed protein in tumor samples strongly suggest that these genes could be oncogenes and hence potential targets for diagnosis and therapy in lung adenocarcinoma.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 16369491   Authors: Li R,Wang H,Bekele BN,Yin Z,Caraway NP,Katz RL,Stass SA,Jiang F
Exact source Table 1
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Organism Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
Source platform HUMAN_GENE_SYMBOL
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NCI-60 cell lines (National Cancer Institute)
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Version history 3.0: First introduced

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