AURKA is one of the downstream targets of MAPK1/ERK2 in pancreatic cancer.
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.
Furukawa
T
T
International Research and Educational Institute for Integrated Medical Sciences, Tokyo Women's Medical University, Tokyo, Japan. furukawa@imcir.twmu.ac.jp
Kanai
N
N
Shiwaku
H O
HO
Soga
N
N
Uehara
A
A
Horii
A
A
D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases; D002460:Cell Line; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D054642:Dual Specificity Phosphatase 6; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000201:enzymology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis / Q000235:genetics
C576917:AURKA protein, human; C576921:AURKB protein, human; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1; C517035:DUSP6 protein, human; D054642:Dual Specificity Phosphatase 6; D017027:Protein Tyrosine Phosphatases