AURKA is one of the downstream targets of MAPK1/ERK2 in pancreatic cancer

T. Furukawa, N. Kanai, H. O. Shiwaku, N. Soga, A. Uehara, A. Horii

Research output: Contribution to journalArticlepeer-review

89 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4831-4839
Number of pages9
JournalOncogene
Volume25
Issue number35
DOIs
Publication statusPublished - 2006 Aug 10

Keywords

  • Aurora
  • Gene expression
  • Kinase
  • Microarray
  • Phosphatase
  • Signal transduction

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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