@article{oai:kanazawa-u.repo.nii.ac.jp:00027558,
 author = {馬場, 智久 and 向田, 直史 and Li, Ying-Yi and Wu, Yu and Tsuneyama, Koichi and Baba, Tomohisa and Mukaida, Naofumi},
 issue = {3},
 journal = {Cancer science},
 month = {Mar},
 note = {We previously demonstrated that the proto-oncogene Pim-3 with serine/ threonine kinase activity was aberrantly expressed in cancer cells but not in the normal cells of the pancreas. In order to elucidate the molecular mechanism underlying aberrant Pim-3 expression in pancreatic cancer cells, we constructed luciferase expression vectors linked to 5′-flanking deletion mutants of the human Pim-3 gene and transfected human pancreatic cancer cells with the resultant vectors. The region up to -264 bp was essential for constitutive Pim-3 gene expression, and the mutation in the Ets-1 binding site (between -216 and -211 bp) reduced luciferase activities. Moreover, Ets-1 mRNA and protein were constitutively expressed together with Pim-3 in human pancreatic cancer cell lines. Chromatin immunoprecipitation assay demonstrated constitutive binding of Ets-1 to the 5′-flanking region of human Pim-3 gene between -249 and -183 bp. Pim-3 promoter activity and its protein expression were induced by transfection with wild type-Ets-1 and were reduced by transfection with dominant negative-Ets-1 or Ets-1 small-interfering RNA (siRNA). Furthermore, dominant negative-Ets-1 and Ets-1 siRNA reduced the amount of Bad phosphorylated at its Ser 112 and induced apoptosis, when they were transfected into human pancreatic cancer cells. Finally, Pim-3 cDNA transfection reversed Ets-1 siRNA-induced increase in apoptosis and decrease in Bad phosphorylation at its Ser 112. These observations would indicate that the transcription factor Ets-1 can induce aberrant Pim-3 expression and subsequently prevent apoptosis in human pancreatic cancer cells. © 2009 Japanese Cancer Association., 金沢大学がん研究所がん病態制御},
 pages = {396--404},
 title = {Essential contribution of Ets-1 to constitutive Pim-3 expression in human pancreatic cancer cells.},
 volume = {100},
 year = {2009}
}