Molecular basis for the induction of vaults by anti-cancer agents, and the role of vaults in resistance to anti-cancer agents.

主拱顶蛋白（MVP）是拱顶核糖核蛋白颗粒的主要成分。虽然在多药耐药中的作用已被提出，但拱顶的生理功能仍不清楚。有报道称，在使用dna损伤剂如阿霉素（ADR）治疗后，MVP水平升高。本研究旨在探讨ADM诱导MVP的分子基础，并探讨MVP在耐药中的潜在作用。ADM增加了MVP蛋白和MVP mRNA的表达量，并增强了MVP启动子的活性。在sw620细胞中引入抗Sp-1的siRNA可降低ADM诱导的MVP表达，通过MVP RNAi下调sw620细胞中MVP的表达可增加细胞对ADM的敏感性，ADM可增强MVP敲除细胞中caspase 3和caspase 8的激活，而在对照细胞中则无此作用。我们的数据表明，癌细胞暴露于dna损伤剂诱导的MVP可能在对化疗药物的耐药性中起重要作用。

The major vault protein(MVP) is the main constituent of the vault ribonucleoprotein particle. Although the role in multidrug resistance has been suggested, the physiological function of vaults remains unclear. It has been reported that MVP levels were elevated after treatment with the DNA-damaging agents such as adriamycin(ADR). The aim of this study was to investigate molecular basis for the induction of MVP by ADM, and to investigate the potential role of MVP in drug resistance. Expression levels of both MVP protein and MVP mRNA were increased by ADM. ADM could also enhance MVP promoter activity. Introduction of siRNA against Sp-1 in SW620cells attenuated the expression of MVP induced by ADM. Down-regulation of MVP expression by MVP RNAi in SW620cells increased the sensitivity of the cells to ADM. Furthermore, ADM enhanced the activation of caspase 3 and caspase 8 in the MVP knock-down cells, but not in control cells. Our data demonstrate that exposure of cancer cells to DNA-damaging agents induces MVP that might have an important role in the resistance to chemotherapeutic agents.