Experimental therapy with 9-[2-(phosphonomethoxy)ethyl]-2,6-diaminopurine (PMEDAP): origin of resistance
Language English Country Czech Republic Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
17579998
PII: file/6134/fb2007a0014.pdf
Knihovny.cz E-resources
- MeSH
- Adenine analogs & derivatives therapeutic use MeSH
- Transcriptional Activation MeSH
- Drug Resistance, Neoplasm * MeSH
- Rats MeSH
- Humans MeSH
- Lymphoma drug therapy genetics MeSH
- Cell Line, Tumor MeSH
- Rats, Sprague-Dawley MeSH
- Multidrug Resistance-Associated Proteins genetics metabolism MeSH
- Antineoplastic Agents therapeutic use MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Neoplasm Transplantation MeSH
- Organ Size MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine MeSH Browser
- ABCC4 protein, human MeSH Browser
- Abcc4 protein, rat MeSH Browser
- ABCC5 protein, human MeSH Browser
- Abcc5 protein, rat MeSH Browser
- Adenine MeSH
- Multidrug Resistance-Associated Proteins MeSH
- Antineoplastic Agents MeSH
The role of MRP4 and MRP5 transporters in the acyclic nucleoside phosphonate PMEDAP efflux was studied in vitro (CCRF-CEM cells) and in vivo (spontaneous transplantable T-cell lymphoma of SD/Cub inbred rats). The increased resistance against the cytostatic agent PMEDAP during longterm treatment was found to be associated with overexpression of MRP4 and MRP5 genes. The course of both gene activation differs significantly. While the MRP5 function is important in the onset of PMEDAP resistance, the intensity of the relative MRP4 gene expression increases rather continuously. Our data indicate cooperative acting of both MRP4 and MRP5 genes during the PMEDAP resistance development.
