Topic
ABCC10
About: ABCC10 is a research topic. Over the lifetime, 34 publications have been published within this topic receiving 1783 citations. The topic is also known as: EST182763 & MRP7.
Papers
TL;DR: Investigation of the ability of lapatinib to reverse tumor multidrug resistance (MDR) due to overexpression of ABC subfamily B member 1 (ABCB1) and ABCsubfamily G member 2 (ABCG2) transporters found it reverses ABCB1- and ABCG2-mediated MDR by directly inhibiting their transport function.
Abstract: Lapatinib is active at the ATP-binding site of tyrosine kinases that are associated with the human epidermal growth factor receptor (Her-1 or ErbB1) and Her-2. It is conceivable that lapatinib may inhibit the function of ATP-binding cassette (ABC) transporters by binding to their ATP-binding sites. The aim of this study was to investigate the ability of lapatinib to reverse tumor multidrug resistance (MDR) due to overexpression of ABC subfamily B member 1 (ABCB1) and ABC subfamily G member 2 (ABCG2) transporters. Our results showed that lapatinib significantly enhanced the sensitivity to ABCB1 or ABCG2 substrates in cells expressing these transporters, although a small synergetic effect was observed in combining lapatinib and conventional chemotherapeutic agents in parental sensitive MCF-7 or S1 cells. Lapatinib alone, however, did not significantly alter the sensitivity of non-ABCB1 or non-ABCG2 substrates in sensitive and resistant cells. Additionally, lapatinib significantly increased the accumulation of doxorubicin or mitoxantrone in ABCB1- or ABCG2-overexpressing cells and inhibited the transport of methotrexate and E217βG by ABCG2. Furthermore, lapatinib stimulated the ATPase activity of both ABCB1 and ABCG2 and inhibited the photolabeling of ABCB1 or ABCG2 with [125I]iodoarylazidoprazosin in a concentration-dependent manner. However, lapatinib did not affect the expression of these transporters at mRNA or protein levels. Importantly, lapatinib also strongly enhanced the effect of paclitaxel on the inhibition of growth of the ABCB1-overexpressing KBv200 cell xenografts in nude mice. Overall, we conclude that lapatinib reverses ABCB1- and ABCG2-mediated MDR by directly inhibiting their transport function. These findings may be useful for cancer combinational therapy with lapatinib in the clinic. [Cancer Res 2008;68(19):7905–14]
395 citations
TL;DR: The drug resistance capabilities of MRP7 are evaluated by analyzing the resistance profiles of two clones of HEK293 cells in which the pump was ectopically expressed and indicate that MRP 7, unlike other MRPs, is a resistance factor for taxanes.
Abstract: The multidrug resistance protein (MRP) family consists of nine members that can be categorized according to whether or not a third (NH2-terminal) membrane-spanning domain is present. Three (MRP1, MRP2, and MRP3) of the four members that have this structural feature are able to confer resistance to natural product anticancer agents. We previously established that MRP7, the remaining family member that has three membrane-spanning domains, possesses the cardinal biochemical activity of MRPs in that it is able to transport amphipathic anions such as 17β-estradiol 17-(β-d-glucuronide). However, the drug resistance profile of the pump has not been determined. In this study, the drug resistance capabilities of MRP7 are evaluated by analyzing the resistance profiles of two clones of HEK293 cells in which the pump was ectopically expressed. MRP7-transfected HEK293 cells exhibited the highest levels of resistance toward docetaxel (9–13-fold). In addition, lower levels of resistance were observed for paclitaxel (3-fold), vincristine (3-fold), and vinblastine (3–4-fold). Consistent with the operation of an ATP-dependent efflux pump, MRP7-transfected cells exhibited reduced accumulation of radiolabeled paclitaxel compared with HEK293 cells transfected with parental plasmid. These results indicate that MRP7, unlike other MRPs, is a resistance factor for taxanes.
187 citations
TL;DR: The determination that MRP7 has the facility for mediating the transport of conjugates such as E(2)17betaG indicates that it is a lipophilic anion transporter involved in phase III (cellular extrusion) of detoxification.
Abstract: Human multidrug resistance protein 7 (MRP7, ABCC10) is a recently described member of the C family of ATP binding cassette proteins (Cancer Lett162:181–191, 2001). However, neither its biochemical activity nor physiological functions have been determined. Here we report the results of investigations of the in vitro transport properties of MRP7 using membrane vesicles prepared from human embryonic kidney 293 cells transfected with MRP7 expression vector. It is shown that expression of MRP7 is specifically associated with the MgATP-dependent transport of 17β-estradiol-(17-β-d-glucuronide) (E217βG). E217βG transport was saturable, with Km andVmax values of 57.8 ± 15 μM and 53.1 ± 20 pmol/mg/min. By contrast, with E217βG, only modest enhancement of LTC4 transport was observed and transport of several other established substrates of MRP family transporters was not detectable to any extent. In accord with the notion that MRP7 has a bipartite substrate binding pocket composed of sites for anionic and lipophilic moieties, transport of E217βG was susceptible to competitive inhibition by both amphiphiles, such as leukotriene C4(Ki(app), 1.5 μM), glycolithocholate 3-sulfate (Ki(app), 34.2 μM) and MK571 (Ki(app), 28.5 μM), and lipophilic agents such as cyclosporine A (Ki(app), 14.4 μM). Of the inhibitors tested, LTC4 was the most potent, in agreement with the possibility that it is a substrate of the pump. The determination that MRP7 has the facility for mediating the transport of conjugates such as E217βG indicates that it is a lipophilic anion transporter involved in phase III (cellular extrusion) of detoxification.
176 citations
TL;DR: Up‐regulation of ABC transporters in HCC occurs prior to chemotherapeutic treatment and is associated with miRNA down‐regulation, providing an indication for miRNA regulation of ABC genes in H CC.
162 citations
TL;DR: The experiments indicate that the resistance capabilities of MRP7 include nucleoside-based agents and a range of natural product anticancer agents that includes nontaxane antimicrotubule agents that are not susceptible to P-glycoprotein-mediated transport and that, unlike MRP1 and MRP2, MRP 7-mediated drug transport does not involve glutathione.
Abstract: Multidrug resistance protein 7 (MRP7; ABCC10) is an ATP-binding cassette transporter which is able to transport amphipathic anions and confer resistance to docetaxel and, to a lesser extent, vincristine and paclitaxel. Whereas some detail on the resistance profile of MRP7 is known, the activities of the pump have not been completely determined. Here, it is shown by the analysis of MRP7-transfected HEK293 cells that, in addition to natural product agents, MRP7 is also able to confer resistance to nucleoside-based agents, such as the anticancer agents cytarabine (Ara-C) and gemcitabine, and the antiviral agents 2',3'-dideoxycytidine and PMEA. Consistent with the operation of an efflux pump, expression of MRP7 reduced the accumulation of Ara-C and PMEA. In addition, MRP7 is also able to confer resistance to the microtubule-stabilizing agent epothilone B. Ectopic expression of MRP7 in mouse embryo fibroblasts deficient in P-glycoprotein and Mrp1 revealed that MRP7 has a broad resistance profile for natural product agents. In this drug-sensitive cellular background, MRP7 conferred high levels of resistance to docetaxel (46-fold), paclitaxel (116-fold), SN-38 (65-fold), daunorubicin (7.5-fold), etoposide (11-fold), and vincristine (56-fold). Buthionine sulfoximine did not attenuate MRP7-conferred resistance to docetaxel or Ara-C. These experiments indicate that the resistance capabilities of MRP7 include nucleoside-based agents and a range of natural product anticancer agents that includes nontaxane antimicrotubule agents that are not susceptible to P-glycoprotein-mediated transport and that, unlike MRP1 and MRP2, MRP7-mediated drug transport does not involve glutathione.
131 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 5 |
| 2020 | 2 |
| 2019 | 2 |
| 2018 | 1 |
| 2017 | 1 |
| 2016 | 1 |