title: Down-regulation of deoxycytidine kinase enhances acquired resistance to gemcitabine in pancreatic cancer.
abstract: BACKGROUND
  The functional roles of deoxycytidine kinase (dCK) in acquired resistance to gemcitabine remain unknown in pancreatic cancer. Here, the functional involvement of dCK in gemcitabine-resistance of pancreatic cancer was investigated.
  
  
  METHODS
  The levels of the dCK gene as well as other gemcitabine-related genes (hENT1, RRM1 and RRM2) were analyzed in gemcitabine-resistant pancreatic cancer cells (GR cells) using quantitative real-time reverse transcription polymerase chain reaction. The effects of inhibition of these genes on sensitivity to gemcitabine were evaluated.
  
  
  RESULTS
  In GR cells, expression of dCK was significantly reduced compared with that of parental cells (p < 0.05). The dCK-targeting siRNA significantly reduced gemcitabine sensitivity (p < 0.01) without affecting cell proliferation. The RRM1- and RRM2-targeting siRNAs increased gemcitabine sensitivity (p < 0.05) and reduced cell proliferation even without gemcitabine treatment. The hENT-targeting siRNA did not affect gemcitabine sensitivity or cell proliferation.
  
  
  CONCLUSIONS
  Down-regulation of dCK specifically enhanced acquired resistance to gemcitabine in pancreatic cancer cells without affecting their proliferation.
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Ohhashi
authors.forename: Kenoki
authors.initials: K
authors.lastname: Ohuchida
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Mizumoto
authors.forename: Hayato
authors.initials: H
authors.lastname: Fujita
authors.forename: Takuya
authors.initials: T
authors.lastname: Egami
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.forename: Hiroki
authors.initials: H
authors.lastname: Toma
authors.forename: Shoko
authors.initials: S
authors.lastname: Sadatomi
authors.forename: Eishi
authors.initials: E
authors.lastname: Nagai
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka