RRC ID 11186
Author Nishio R, Tsuchiya H, Yasui T, Matsuura S, Kanki K, Kurimasa A, Hisatome I, Shiota G.
Title Disrupted plasma membrane localization of equilibrative nucleoside transporter 2 in the chemoresistance of human pancreatic cells to gemcitabine (dFdCyd).
Journal Cancer Sci.
Abstract Although the nucleoside pyrimidine analogue gemcitabine is the most effective single agent in the palliation of advanced pancreatic cancer, cellular resistance to gemcitabine treatment is a major problem in the clinical scene. To clarify the molecular mechanisms responsible for chemoresistance to gemcitabine, mRNA expression of the key enzymes including cytidine deaminase (CDA), deoxycytidine kinase (dCK), 5'-nucleotidase (NT5), equilibrative nucleoside transporter 1 and 2 (ENT1 and ENT2), dCMP deaminase (dCMPK), ribonucleotide reductase M1 and M2 (RRM1 and RRM2), thymidylate synthase (TS) and CTP synthase (CTPS) was examined. The interacellular uptake of gemcitabine was greatly impaired in the chemoresistant cell lines due to dysfunction of ENT1 and ENT2. Protein expression of ENT1 and ENT2 and their protein coding sequences were not altered. Immunohistochemical and western blot analyses revealed that localization of ENT2 on the plasma membrane was disrupted. These data suggest that the disrupted localization of ENT2 is one of causes of the impaired uptake of gemcitabine, resulting in a gain of chemoresistance to gemcitabine.
Volume 102(3)
Pages 622-9
Published 2011-3
DOI 10.1111/j.1349-7006.2010.01837.x
PMID 21205085
MeSH Antimetabolites, Antineoplastic / pharmacology* Cell Line, Tumor Cell Membrane / chemistry Deoxycytidine / analogs & derivatives* Deoxycytidine / metabolism Deoxycytidine / pharmacology Drug Resistance, Neoplasm Equilibrative Nucleoside Transporter 1 / analysis Equilibrative-Nucleoside Transporter 2 / analysis* Humans Oligonucleotide Array Sequence Analysis Pancreatic Neoplasms / chemistry Pancreatic Neoplasms / drug therapy* Pancreatic Neoplasms / pathology
IF 4.751
Times Cited 7
Human and Animal Cells MIA Paca2 (RCB2094)