ATP-binding cassette (ABC) transporters, alongside ion channels and aquaporins, are ubiquitous membrane-bound proteins that move substrates across extra and intra cellular membranes. Multidrug resistance-associated protein 1 (MRP1) is a member of the superfamily of ATP-binding cassette (ABC) transporters, and in humans is encoded by the ABCC1 gene. In addition to endogenous substrate exchange, ABC transporters also participate in the movement of drugs and chemicals across cell surface and cellular organelle membranes, suggesting that defects in these genes are of great importance in cancer therapy and pharmacokinetics. In fact, MRP1 was initially identified due to its ability to yield multidrug resistance in lung cancer cells. MRP1 is one of many genes that may alter a tumor cell to expel cancer drugs and deem them ineffective. Specifically, MRP1 acts as a pump, disposing of cytotoxic chemicals from tumor cells. Drug resistance in chemotherapy is a constant hurdle in the pharmaceutical world; therefore a way to inhibit or understand MRP1 is much needed.
Cancer cells utilize specific fuel sources and often times alter their cellular pathways to metabolize nutrients differently than non-cancerous cells. By identifying and disrupting key players in a cancer cell’s cellular pathway, there is potential to halt tumor cell proliferation in an isolated manner. Koshkin et al recently used a Novus’ MRP1 Antibody (IU2H10) to measure MDR (multi drug resistance) activity and transporter expression in MCF7 cells via Flow Cytometry (3). It has been previously established that the MRP1 antibody is linked to MCF7 specific MDR – and their results revealed that moving from 2D to 3D cancer cell models increased modification of MDR. Chen et al tested the uptake of a selective antitumor agent SN 28049, using the MRP1 Antibody (IU2H10) to test whether rate of uptake changed with expression of MRP1 or a p-glycoprotein (4). Overall, only a slight change of uptake rate was witnessed – however SN 28049 was found to be successful in retention and uptake for Co38P cancer cells. Other groups have also employed an MRP1 antibody to test the efficacy of new methods for following the interaction of membrane proteins at a cellular level. In the case of Kurihara et al, a reflectometric interference spectroscopy (RIfS)-based sensor was created to closely follow the activity of MRP1 (5). Ultimately it was concluded that RIfS is an effective method of following specific binding events of biologically active membrane proteins – free of labeling.
The Massachusetts Institute of Technology recently announced an exciting approach to overcome drug resistance in cancer therapy where their researchers created gold nanoparticles coated with strands of DNA complementary to the sequence of MRP1 mRNA. These nanoparticles would not only prevent more MRP1 from being produced, but would also release an embedded drug into the cell environment. New advancements such as this would not be possible without the use of MRP1 antibodies as an investigatory and diagnostic tool.
Novus Biologicals offers MRP1 reagents for your research needs including:
