Induction of MRP5 and SMRP mRNA by adriamycin exposure and its overexpression in human lung cancer cells resistant to Adriamycin

Citation
M. Yoshida et al., Induction of MRP5 and SMRP mRNA by adriamycin exposure and its overexpression in human lung cancer cells resistant to Adriamycin, INT J CANC, 94(3), 2001, pp. 432-437
Citations number
38
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
INTERNATIONAL JOURNAL OF CANCER
ISSN journal
0020-7136 → ACNP
Volume
94
Issue
3
Year of publication
2001
Pages
432 - 437
Database
ISI
SICI code
0020-7136(20011101)94:3<432:IOMASM>2.0.ZU;2-P
Abstract
Acquired anticancer drug resistance in cancer cells is often a result of an increase in levels of the ATP binding cassette (ABC) transporters that exp ort anticancer drugs from cancer cells, suggesting that anticancer drugs ma y induce genes that mediate drug resistance in cancer cells. In this study, the induction of anticancer drug transporter gene expression by Adriamycin was examined in human lung cancer cell lines. Increased expression of MDR1 , MRP5- and SMRP mRNA was observed 48 hr after the initiation of Adriamycin exposure in human lung cancer PC-14 cells and cisplatin-resistant PC-14/CD DP cells, in a dose-dependent manner as measured by TaqMan real-time RT-PCR . The levels of MRP-1, MRP2 and LRP mRNA were not altered by Adriamycin exp osure. The biologic functions of the MRP5 and SMRP genes have not been full y clarified. To elucidate the relationship between Adriamycin resistance an d MRP5 and SMRP, mRNA levels of MRP5 and SMRP in Adriamycin-resistant cell lines were compared with the parental cells. Increased expression of MRPS a nd SMRP mRNA was observed in all 3 cell lines (SBC-3/ADM, AdR MCF7 and K562 /ADM) by Northern blot analysis and RNase protection assay. These results s uggest that subacute exposure of lung cancer cells to Adriamycin induced MR P5 and SMRP and that long-term exposure with Adriamycin selected the MRP5- and SMRP-overexpressing lung cancer cells. MRP5 and SMRP is a candidate mol ecule for acquired Adriamycin resistance in addition to MDR1. (C) 2001 Wile y-Liss, Inc.