title: Disruption of the murine major vault protein (MVP/LRP) gene does not induce hypersensitivity to cytostatics.
abstract: Vaults are ribonucleoprotein particles with a distinct structure and a high degree of conservation between species. Although no function has been assigned to the complex yet, there is some evidence for a role of vaults in multidrug resistance. To confirm a direct relation between vaults and multidrug resistance, and to investigate other possible functions of vaults, we have generated a major vault protein (MVP/lung resistance-related protein) knockout mouse model. The MVP(-/-) mice are viable, healthy, and show no obvious abnormalities. We investigated the sensitivity of MVP(-/-) embryonic stem cells and bone marrow cells derived from the MVP-deficient mice to various cytostatic agents with different mechanisms of action. Neither the MVP(-/-) embryonic stem cells nor the MVP(-/-) bone marrow cells showed an increased sensitivity to any of the drugs examined, as compared with wild-type cells. Furthermore, the activities of the ABC-transporters P-glycoprotein, multidrug resistance-associated protein and breast cancer resistance protein were unaltered on MVP deletion in these cells. In addition, MVP wild-type and deficient mice were treated with the anthracycline doxorubicin. Both groups of mice responded similarly to the doxorubicin treatment. Our results suggest that MVP/vaults are not directly involved in the resistance to cytostatic agents.
authors.affiliation: Department of Hematology, Erasmus University Rotterdam, 3015 GE Rotterdam, The Netherlands.
authors.forename: Marieke H
authors.initials: MH
authors.lastname: Mossink
authors.forename: Arend
authors.initials: A
authors.lastname: van Zon
authors.forename: Erna
authors.initials: E
authors.lastname: Fränzel-Luiten
authors.forename: Martijn
authors.initials: M
authors.lastname: Schoester
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Kickhoefer
authors.forename: George L
authors.initials: GL
authors.lastname: Scheffer
authors.forename: Rik J
authors.initials: RJ
authors.lastname: Scheper
authors.forename: Pieter
authors.initials: P
authors.lastname: Sonneveld
authors.forename: Erik A C
authors.initials: EA
authors.lastname: Wiemer
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D001854:Bone Marrow Cells / Q000187:drug effects / Q000502:physiology; D002678:Chimera; D004317:Doxorubicin / Q000494:pharmacology / Q000633:toxicity; D018432:Drug Resistance, Multiple / Q000235:genetics* / Q000502:physiology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology; D020394:Vault Ribonucleoprotein Particles / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D000099187:Major Vault Protein
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein