Gene Set: ZHONG_RESPONSE_TO_AZACITIDINE_AND_TSA_DN

Standard name ZHONG_RESPONSE_TO_AZACITIDINE_AND_TSA_DN
Systematic name M3988
Brief description Genes down-regulated in 3 out of 4 NSCLC cell lines (non-small cell lung cancer) after treatment with azacitidine [PubChem=9444] and TSA [PubChem=5562].
Full description or abstract Lung cancer is the leading cause of cancer-related deaths in the United States due, in large part, to the lack of early detection methods. Lung cancer arises from a complex series of genetic and epigenetic changes leading to uncontrolled cell growth and metastasis. Unlike genetic changes, epigenetic changes, such as DNA methylation and histone acetylation, are reversible with currently available pharmaceuticals and are early events in lung tumorigenesis detectable by non-invasive methods. In order to better understand how epigenetic changes contribute to lung cancer, and to identify new disease biomarkers, we combined pharmacologic inhibition of DNA methylation and histone deacetylation in non-small cell lung cancer (NSCLC) cell lines, with genome-wide expression profiling. Of the more than 200 genes upregulated by these treatments, three of these, neuronatin, metallothionein 3 and cystatin E/M, were frequently hypermethylated and transcriptionally downregulated in NSCLC cell lines and tumors. Interestingly, four other genes, cylindromatosis, CD9, activating transcription factor 3 and oxytocin receptor, were dominantly regulated by histone deacetylation and were also frequently downregulated in lung tumors. The majority of these genes also suppressed NSCLC growth in culture when ectopically expressed. This study therefore reveals new putative NSCLC growth regulatory genes and epigenetic disease biomarkers that may enhance early detection strategies and serve as therapeutic targets.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 17043644   Authors: Zhong S,Fields CR,Su N,Pan YX,Robertson KD
Exact source Table S1: Fold change < 1 (green)
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Organism Homo sapiens
Contributed by Leona Saunders (MSigDB Team)
Source platform AFFY_HG_U133
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