Human Gene Set: MISSIAGLIA_REGULATED_BY_METHYLATION_DN


Standard name MISSIAGLIA_REGULATED_BY_METHYLATION_DN
Systematic name M6866
Brief description Genes down-regulated in PaCa44 and CFPAC1 cells (pancreatic cancer) after treatment with decitabine [PubChem=451668], a DNA hypomethylating agent similar to azacitidine [PubChem=9444].
Full description or abstract Alteration of methylation status has been recognized as a possible epigenetic mechanism of selection during tumorigenesis in pancreatic cancer. This type of cancer is characterized by poor prognosis partly due to resistance to conventional drug treatments. We have used microarray technology to investigate the changes in global gene expression observed after treatment of different pancreatic cancer cell lines with the methylase inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR). We have observed that this agent is able to inhibit to various degrees the growth of three pancreatic cancer cell lines. In particular, this inhibition was associated with induction of interferon (IFN)-related genes, as observed in other tumour types. Thus, expression of STAT1 seems to play a key role in the cellular response to treatment with the cytosine analogue. Moreover, we found increased p21(WAF1) and gadd45A expression to be associated with the efficacy of the treatment; this induction may correlate with activation of the IFN signalling pathway. Expression of the p16(INK) protein was also linked to the ability of cells to respond to 5-aza-CdR. Finally, genome-wide demethylation induced sensitization that significantly increased response to further treatment with various chemotherapy agents.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 15637593   Authors: Missiaglia E,Donadelli M,Palmieri M,Crnogorac-Jurcevic T,Scarpa A,Lemoine NR
Exact source Table 2S
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Source species Homo sapiens
Contributed by Leona Saunders (MSigDB Team)
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identifier namespace		 HUMAN_GENE_SYMBOL
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Version history 3.0: First introduced

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