RT Journal Article
SR Electronic
T1 Involvement of ABC Transporters in Chemosensitivity of Human Renal Cell Carcinoma, and Regulation of MRP2 Expression by Conjugated Bilirubin
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 2729
OP 2735
VO 25
IS 4
A1 NOMURA, MASAAKI
A1 MATSUNAMI, TOSHIO
A1 KOBAYASHI, KAYOKO
A1 UCHIBAYASHI, TADAO
A1 KOSHIDA, KIYOSHI
A1 TANAKA, MOTOHIRO
A1 NAMIKI, MIKIO
A1 MIZUHARA, YASUHARU
A1 AKIBA, TETSUO
A1 YOKOGAWA, KOICHI
A1 MORITANI, SHUZO
A1 MIYAMOTO, KEN-ICHI
YR 2005
UL http://ar.iiarjournals.org/content/25/4/2729.abstract
AB In this study, the involvement of ATP-binding cassette (ABC) transporters in in vitro chemosensitivity of surgically removed human renal cell carcinomas was investigated. The relative expression levels of transporter mRNAs in the renal tumors from 13 patients were similar to those in the surrounding normal kidney tissues. Five renal cell carcinomas cultured successfully in vitro for 14 days showed significantly decreased expression of multi-drug resistance-associated proteins 2 and 6 (MRP2 and MRP6) mRNAs. In vitro chemosensitivity testing of the same specimens using the collagen-gel matrix assay indicated that some anticancer drugs were effective, especially cisplatin, which is an MRP2 substrate. MRP2 mRNA expression in renal carcinoma was significantly increased when cells were cultured in the presence of conjugated bilirubin. In an established renal proximal tubule epithelial cell line (RPTEC), conjugated bilirubin increased MRP2 expression at the mRNA and protein levels, and decreased the cisplatin sensitivity of the cells. These results indicate that MRP2 expression in renal cell carcinoma may be regulated by conjugated bilirubin in the body and decreased during in vitro culture. Thus, the effectiveness of anticancer drugs selected on the basis of in vitro chemosensitivity testing of clinical cancers may be overestimated. Copyright© 2005 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved