Experimental therapy with 9-[2-(phosphonomethoxy)ethyl]-2,6-diaminopurine (PMEDAP): origin of resistance.
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.
Zápotocký
M
M
Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic. Michal.Zapotocky@fnmotol.cz
Hanzalová
J
J
Starková
J
J
Votruba
I
I
Holý
A
A
Otová
B
B
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D009368:Neoplasm Transplantation; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D015533:Transcriptional Activation
D000225:Adenine; D000970:Antineoplastic Agents; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C073492:ABCC4 protein, human; C120809:ABCC5 protein, human; C489542:Abcc4 protein, rat; C492375:Abcc5 protein, rat; C059499:9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine