Human equilibrative nucleoside transporter 1 is associated with the chemosensitivity of gemcitabine in human pancreatic adenocarcinoma and biliary tract carcinoma cells.

Authors:
  • TITakashi Ishikawa
    Takashi Ishikawa
  • YIYasushi Ichikawa
    Yasushi Ichikawa
  • KTKoichi Taniguchi
    Koichi Taniguchi
  • RMRyusei Matsuyama
    Ryusei Matsuyama
  • MUMichio Ueda
    Michio Ueda
  • YFYoshiro Fujii
    Yoshiro Fujii
  • IEItaru Endo
    Itaru Endo
  • STShinji Togo
    Shinji Togo
  • PDPeter V. Danenberg
    Peter V. Danenberg
  • HSHiroshi Shimada
    Hiroshi Shimada
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Abstract
Gemcitabine has been one of the most commonly used agents for pancreatic adenocarcinoma chemotherapy, but the determinants of the sensitivity of and resistance to this agent are not yet fully understood. In this study with pancreatic carcinoma and biliary tract carcinoma cell lines, we examined the gene expression levels of nucleotide transporters and others related to the metabolism of gemcitabine in the light of sensitivity to this agent. Quantitative RT-PCR demonstrated that one of the nucleotide transporter genes; human equilibrative nucleoside transporter 1 (hENT1) was associated with the sensitivity to gemcitabine as represented by IC50, while the other genes for nucleotide transporter and metabolism were not. We conclude that increased hENT1 expression is a most important determinant of gemcitabine sensitivity at least in an in vitro study.