| RRC ID |
11186
|
| 著者 |
Nishio R, Tsuchiya H, Yasui T, Matsuura S, Kanki K, Kurimasa A, Hisatome I, Shiota G.
|
| タイトル |
Disrupted plasma membrane localization of equilibrative nucleoside transporter 2 in the chemoresistance of human pancreatic cells to gemcitabine (dFdCyd).
|
| ジャーナル |
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.
|
| 巻・号 |
102(3)
|
| ページ |
622-9
|
| 公開日 |
2011-3-1
|
| 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 |
4.966
|
| 引用数 |
11
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
MIA Paca2(RCB2094) |
