Human equilibrative nucleoside transporter 1 is associated with the chemosensitivity of gemcitabine in human pancreatic adenocarcinoma and biliary tract carcinoma cells.
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.
Mori
Ryutaro
R
Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan. rmori@ck2.so-net.ne.jp
Ishikawa
Takashi
T
Ichikawa
Yasushi
Y
Taniguchi
Koichi
K
Matsuyama
Ryusei
R
Ueda
Michio
M
Fujii
Yoshiro
Y
Endo
Itaru
I
Togo
Shinji
S
Danenberg
Peter V
PV
Shimada
Hiroshi
H
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001661:Biliary Tract Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D003564:Cytidine Deaminase / Q000096:biosynthesis / Q000235:genetics; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003842:Deoxycytidine Kinase / Q000096:biosynthesis / Q000235:genetics; D033721:Equilibrative Nucleoside Transporter 1 / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012262:Ribonucleoside Diphosphate Reductase / Q000096:biosynthesis / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D033721:Equilibrative Nucleoside Transporter 1; D012333:RNA, Messenger; C438649:SLC29A1 protein, human; D025521:Tumor Suppressor Proteins; D003841:Deoxycytidine; C093713:ribonucleotide reductase M2; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D003842:Deoxycytidine Kinase; D003564:Cytidine Deaminase; D000093542:Gemcitabine