title: Human equilibrative nucleoside transporter 1, as a predictor of 5-fluorouracil resistance in human pancreatic cancer.
abstract: BACKGROUND
  The purpose of this study was to find a novel biomarker to predict 5-fluorouracil (5-FU) or gemcitabine (2',2'-difluoro-deoxycytidine) sensitivity in pancreatic cancer.
  
  
  METHODS
  The relationship between 5-FU and gemcitabine sensitivity and the mRNA levels of human equilibrative nucleoside transporter 1 (hENT1), thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) was investigated using seven types of human pancreatic carcinoma cell line (AsPC1, BxPC3, MiaPaCa-2, PSN1, Panc1, PCI6, and KMP-4). Quantitative mRNA expression was measured by LightCycler. A [3H] gemcitabine cellular uptake assay was performed to examine the inhibition of hENT1 by nitrobenzylmercaptoprine ribonucleoside (NBMPR).
  
  
  RESULTS
  The expression levels of hENT1 mRNA significantly correlated with the IC50 value of 5-FU in all seven lines and also correlated with gemcitabine resistance in six lines (except AsPC1). No significant association was observed between TS or DPD mRNA levels and 5-FU sensitivity. In the PSN1 cells, [3H] gemcitabine uptake via hENT1 was significantly inhibited by NBMPR, and 5-FU sensitivity was significantly increased when the cells were pretreated with NBMPR.
  
  
  CONCLUSIONS
  Our results suggest that hENT1 plays an important role in 5-FU resistance and that hENT1 mRNA levels might be a useful marker to predict 5-FU sensitivity in pancreatic cancer.
authors: Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University E2, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Masanori
authors: M
authors: Tsujie
authors: Shoji
authors: S
authors: Nakamori
authors: Shin
authors: S
authors: Nakahira
authors: Yuji
authors: Y
authors: Takahashi
authors: Nobuyasu
authors: N
authors: Hayashi
authors: Jiro
authors: J
authors: Okami
authors: Hiroaki
authors: H
authors: Nagano
authors: Keizo
authors: K
authors: Dono
authors: Koji
authors: K
authors: Umeshita
authors: Masato
authors: M
authors: Sakon
authors: Morito
authors: M
authors: Monden
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D033721:Equilibrative Nucleoside Transporter 1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D033721:Equilibrative Nucleoside Transporter 1; D012333:RNA, Messenger; C438649:SLC29A1 protein, human; D003841:Deoxycytidine; D005472:Fluorouracil; D000093542:Gemcitabine