title: Induction of P-glycoprotein expression on the plasma membrane of human melanoma cells.
abstract: Melanoma cells exhibit, both in vivo and in vitro, intrinsic drug resistance to various chemotherapeutic agents. Cultured human melanoma cells (M14) intrinsically express significant amounts of multidrug resistance-related protein (MRP1) and P-glycoprotein (P-gp) in the Golgi apparatus, but do not express these drug transporters on the plasma membrane. A panel of multidrug resistant (MDR) melanoma cell lines (M14Dx), showing different degrees of resistance to doxorubicin (DOX), were isolated. In M14Dx lines, the appearance of surface P-gp, but not of MRP1 or lung resistance related protein (LRP), occurred in cells grown in the presence of DOX concentrations higher than 60 nM. Furthermore, P-gp levels appeared to be dose-dependent. Flow cytometry, laser scanning confocal microscopy and cytotoxicity studies demonstrated that the activity of the drug extrusion system was related to both surface P-gp expression and resistance to DOX. In conclusion, P-gp, but not MRP1 or LRP, might play a pivotal role in the pharmacologically-induced MDR phenotype of melanoma cells.
authors.affiliation: Laboratorio di Ultrastrutture, Istituto Superiore di Sanità, Rome, Italy. molinari@iss.it
authors.forename: A
authors.initials: A
authors.lastname: Molinari
authors.forename: L
authors.initials: L
authors.lastname: Toccacieli
authors.forename: A
authors.initials: A
authors.lastname: Calcabrini
authors.forename: M
authors.initials: M
authors.lastname: Diociaiuti
authors.forename: M
authors.initials: M
authors.lastname: Cianfriglia
authors.forename: G
authors.initials: G
authors.lastname: Arancia
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology*; D018528:ATP-Binding Cassette Transporters / Q000502:physiology; D002462:Cell Membrane / Q000737:chemistry; D004317:Doxorubicin / Q000493:pharmacokinetics; D019008:Drug Resistance, Neoplasm; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011971:Receptors, Immunologic / Q000502:physiology; D014407:Tumor Cells, Cultured
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D004317:Doxorubicin; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011971:Receptors, Immunologic