| First Author | Mossink MH | Year | 2002 |
| Journal | Cancer Res | Volume | 62 |
| Issue | 24 | Pages | 7298-304 |
| PubMed ID | 12499273 | Mgi Jnum | J:80831 |
| Mgi Id | MGI:2447259 | Citation | Mossink MH, et al. (2002) Disruption of the murine major vault protein (MVP/LRP) gene does not induce hypersensitivity to cytostatics. Cancer Res 62(24):7298-304 |
| abstractText | 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. |
