| Literature DB >> 17996297 |
Xing-Xiang Peng1, Zhi Shi, Vijaya L Damaraju, Xiao-Cong Huang, Gary D Kruh, Hsiang-Chun Wu, Ying Zhou, Amit Tiwari, Liwu Fu, Carol E Cass, Zhe-Sheng Chen.
Abstract
To investigate the mechanism of cellular resistance to 6-MP, we established a 6-MP resistant cell line (CEM-MP5) by stepwise selection of the human T-lymphoblastic leukemia cell line (CEM). CEM-MP5 cells were about 100-fold resistant to 6-MP compared with parental CEM cells. Western blot analysis demonstrated that multidrug resistant protein 4 (MRP4) was increased in CEM-MP5 cells, whereas the levels of the nucleoside transporters hENT1, hCNT2 and hCNT3 were decreased compared with those of parental CEM cells. Consistent with the operation of an efflux pump, accumulation of [14C]6-MP and/or its metabolites was reduced, and ATP-dependent efflux was increased in CEM-MP5 cells. Taken together these results showed that up-regulation of MRP4 and down-regulation of influx transporters played a major role in 6-MP resistance of CEM-MP5 cells.Entities:
Mesh：
Substances：
Year: 2007 PMID： 17996297 DOI： 10.1016/j.leukres.2007.09.015
Source DB: PubMed Journal: Leuk Res ISSN： 0145-2126 Impact factor: 3.156