Systematic name M7339
Brief description Genes down-regulated in PCI-35 cells (pancreatic cancer, lack endogenous DUSP6 [GeneID=1848]) upon expression of DUSP6 off an adenoviral vector.
Full description or abstract DUSP6/MKP-3, a specific inhibitor of MAPK1/ERK2, frequently loses its expression in primary pancreatic cancer tissues. This evidence suggests that constitutive activation of MAPK1 synergistically induced by frequent mutation of KRAS2 and the loss of function of DUSP6 plays key roles in pancreatic carcinogenesis and progression. By profiling of gene expressions associated with downregulation of MAPK1 induced by exogenous overexpression of DUSP6 in pancreatic cancer cells, we found that AURKA/STK15, the gene encoding Aurora-A kinase, which plays key roles in cellular mitosis, was among the downregulated genes along with its related genes, which included AURKB, TPX2 and CENPA. An association of expression and promoter activity of AURKA with MAPK activity was verified. Knockdown of ETS2 resulted in a reduction of AURKA expression. These results indicate that AURKA is a direct target of the MAPK pathway and that its overexpression in pancreatic cancer is induced by hyperactivation of the pathway, at least via ETS2.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 16532023   Authors: Furukawa T,Kanai N,Shiwaku HO,Soga N,Uehara A,Horii A
Exact source Table 2AS
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(show 2 gene sets from the same authors)
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Organism Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
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Version history 3.0: First introduced

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