A possible role for multidrug resistance-associated protein in the secretion of basic fibroblast growth factor by osteogenic sarcoma cell line (MG-63).
Basic fibroblast growth factor (bFGF) lacks signal sequence and therefore the mechanism of its secretion is unknown. Multidrug resistance-associated protein (MRP) has been shown to transport a variety of molecules. Therefore, in this study we examined the role of MRP in the secretion of bFGF by osteogenic sarcoma MG-63 cells which spontaneously secrete bFGF. We show that MG-63 cells express MRP both at the protein and at the mRNA level. Furthermore, probenecid (a putative inhibitor of transport activity of MRP), in a concentration-dependent manner, inhibited secretion of bFGF from MG-63 cells with concomitant increase in intracellular contents of bFGF. These results suggest that MRP may have a possible role in the secretion of bFGF.
Aggarwal
S
S
Division of Basic and Clinical Immunology, University of California, Irvine, CA 92697, USA.
Gupta
S
S
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism / Q000502:physiology*; D018432:Drug Resistance, Multiple; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism*; D011339:Probenecid / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012076:Renal Agents / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D018528:ATP-Binding Cassette Transporters; D016222:Fibroblast Growth Factor 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D011339:Probenecid; D012333:RNA, Messenger; D012076:Renal Agents