title: Comparison of chemotherapeutic drug resistance in cells transfected with canine ABCG2 or feline ABCG2.
abstract: ABCG2 (ATP binding cassette subfamily G, member 2) mediates resistance to a variety of cytotoxic agents. Although human ABCG2 is well characterized, the function of canine ABCG2 has not been studied previously. Feline ABCG2 has an amino acid substitution in the adenosine triphosphate-binding domain that decreases its transport capacity relative to human ABCG2. Our goal was to compare canine ABCG2-mediated chemotherapeutic drug resistance to feline ABCG2-mediated chemotherapeutic drug resistance. HEK-293 cells stably transfected with plasmid containing canine ABCG2, feline ABCG2 or no ABCG2 were exposed to carboplatin, doxorubicin, mitoxantrone, toceranib or vincristine, and cell survival was subsequently determined. Canine ABCG2 conferred a greater degree of chemotherapy resistance than feline ABCG2 for mitoxantrone. Neither canine nor feline ABCG2 conferred resistance to doxorubicin, vincristine or toceranib. Canine, but not feline, ABCG2 conferred resistance to carboplatin, a drug that is not reported to be a substrate for ABCG2 in other species.
authors.affiliation: Program in Individualized Medicine, Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Lewis
authors.affiliation: Program in Individualized Medicine, Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Fidel
authors.affiliation: Program in Individualized Medicine, Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Dassanayake
authors.affiliation: Program in Individualized Medicine, Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Court
authors.affiliation: Program in Individualized Medicine, Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USA.
authors.forename: N S
authors.initials: NS
authors.lastname: Burke
authors.affiliation: Program in Individualized Medicine, Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Mealey
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016190:Carboplatin / Q000494:pharmacology; D002415:Cats; D002470:Cell Survival / Q000187:drug effects; D004285:Dogs; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D057809:HEK293 Cells; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008942:Mitoxantrone / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D014162:Transfection; D014750:Vincristine / Q000494:pharmacology
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; C464577:toceranib phosphate; D014750:Vincristine; D004317:Doxorubicin; D016190:Carboplatin; D008942:Mitoxantrone
keywords: ABCG2; breast cancer resistance protein; canine; chemotherapy resistance; feline