Disruption of the murine major vault protein (MVP/LRP) gene does not induce hypersensitivity to cytostatics
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.
|Keywords||Animals, Antineoplastic Agents/*pharmacology/toxicity, Bone Marrow Cells/drug effects/physiology, Chimera, Doxorubicin/pharmacology/toxicity, Drug Resistance, Multiple/*genetics/physiology, Drug Resistance, Neoplasm/genetics, Mice, Mice, Inbred C57BL, Mice, Knockout, Research Support, Non-U.S. Gov't, Stem Cells/drug effects/physiology, Vault Ribonucleoprotein Particles/deficiency/*genetics/physiology|
Mossink, M.H., van Zon, A., Fränzel-Luiten, A.A., Schoester, M., Kickhoefer, V.A., Scheffer, G.L., … Wiemer, E.A.C.. (2002). Disruption of the murine major vault protein (MVP/LRP) gene does not induce hypersensitivity to cytostatics. Cancer Research. Retrieved from http://hdl.handle.net/1765/10037