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
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.