Association between expression of the MRP3 gene and exposure to platinum drugs in lung cancer.
To investigate the roles played by the multidrug resistance-associated protein (MRP1) homologues MRP3 and MRP4 in resistance to platinum drugs, we examined steady-state levels of mRNA for both MRP3 and MRP4 in normal lung and lung cancer specimens as well as peripheral mononuclear cells (PMN) after platinum drug exposure. MRP3 and MRP4 gene expression levels were monitored in the PMN of 10 previously untreated lung cancer patients within 24 hr after carboplatin (CBDCA) administration. Expression levels for both genes were also examined in 80 autopsy samples (40 primary tumors and 40 corresponding normal lung tissues) from 40 patients with lung cancer. MRP3 and MRP4 gene expression levels were assessed by quantitative reverse transcription-polymerase chain reaction. MRP3 expression levels in the PMN rose rapidly within 24 hr after administration of CBDCA, whereas MRP4 expression levels remained the same. Furthermore, MRP3 expression levels in normal lung and tumor tissues from autopsy samples that had been exposed to platinum drugs while the patients were alive were significantly higher than those in unexposed tissues, but again MRP4 expression levels remained the same. These results suggest that platinum drugs and/or the physiological stress response to xenobiotics induce expression of the MRP3 gene.
Oguri
T
T
Second Department of Internal Medicine, Hiroshima University School of Medicine, Hiroshima, Japan. oguri@mcai.med.hiroshima-u.ac.jp
Isobe
T
T
Fujitaka
K
K
Ishikawa
N
N
Kohno
N
N
D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D027321:Anion Transport Proteins; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016190:Carboplatin / Q000494:pharmacology*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018528:ATP-Binding Cassette Transporters; D027321:Anion Transport Proteins; D000970:Antineoplastic Agents; D016190:Carboplatin; D002352:Carrier Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger