Induction ofMRP5 andSMRP mRNA by adriamycin exposure and its overexpression in human lung cancer cells resistant to adriamycin

MRP5b/SMRP mRNA is Highly Expressed in Metallothionein- Deficient Mouse Liver

“…We previously reported that MRP5 has two variants, MRP5a/ MRP5 and MRP5b/SMRP, and since MRP5b was preferentially expressed in liver and skeletal muscle, we speculated that the long fragment expressed in MT-null mouse liver was MRP5b/SMRP. We recently found that adriamycin inducees both MRP5a/ MRP5 and MRP5b/SMRP in lung cancer cell lines and that these MRP5s are over-expressed in adriamycin-resistant cell lines, 14) and in this study we found that SMRP is expressed in the liver of the MT-I, -II null mice. Although the physiological function of MRP5s remains unknown, MRP5b/SMRP may play a role in the detoxification of xenobiotics by these mice instead of MT.…”

The multidrug resistance protein 5 (ABCC5) confers resistance to 5-fluorouracil and transports its monophosphorylated metabolites

“…Treatment of PC-14 and PC-14/ cisplatin cells with Adriamycin resulted in an induction of MRP5 and the splice variant. An increased expression of both MRP5 and SMRP transcripts were also observed in three Adriamycin-selected resistant cell lines (25). Clinical studies of patients after long-term treatment with cisplatin indicated that expression of MRP5 and SMRP mRNAs was elevated in both normal lung tissue and lung tumors even though 24-hours exposure of cells in culture did not increase MRP5 transcripts (26).…”

“…Points , mean; bars , FSE of three independent experiments measured in triplicate; *, significant reduction (f2-fold) in drug accumulation was observed at the data points as determined by Student's t test (P V 0.05). Non -small cell lung cancer PC-14, selected for resistance to cisplatin, were reported to express a MRP5 splice variant called SMRP (25). Treatment of PC-14 and PC-14/ cisplatin cells with Adriamycin resulted in an induction of MRP5 and the splice variant.…”

Drug Efflux Transporter Multidrug Resistance-Associated Protein 5 Affects Sensitivity of Pancreatic Cancer Cell Lines to the Nucleoside Anticancer Drug 5-Fluorouracil

“…Novel strategies that use combinations of inhibitor substances may include yet unknown substrates for this transporter. In addition, we cannot rule out the possibility that these transporters are regulated as part of a multifactorial cellular adaptation mechanism because transporter up-regulation has also been observed when cells adapt to drugs that are not specific substrates for these transporter proteins (Yoshida et al, 2001;P.K.N. and C.A.R., unpublished data).…”