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vault 成分 MVP、TEP1 和 vPARP 的表达谱及其与卵巢癌中其他多药耐药蛋白的相关性。

Expression profiles of vault components MVP, TEP1 and vPARP and their correlation to other multidrug resistance proteins in ovarian cancer.

机构信息

Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznań, Poland.

出版信息

Int J Oncol. 2013 Aug;43(2):513-20. doi: 10.3892/ijo.2013.1975. Epub 2013 Jun 5.

Abstract

Vaults are cytoplasmic ribonucleoprotein particles composed of three proteins (MVP, TEP1, vPARP) and vault‑associated RNAs (vRNAs). Although the cellular functions of vaults remain unclear, vaults are strongly linked to the development of multidrug resistance (MDR), the major obstacle to the efficient treatment of cancers. Available published data suggest that vaults and their components are frequently upregulated in broad variety of multidrug-resistant cancer cell lines and tumors of different histological origin. Here, we provide detailed analysis of vault protein expression in post-surgery ovarian cancer samples from patients that were not exposed to chemotherapy. Our analysis suggests that vault proteins are expressed in the ovaries of healthy individuals but their expression in cancer patients is changed. Specifically, MVP, TEP1 and vPARP mRNA levels are significantly decreased in cancer samples with tendency of lower expression in higher-grade tumors. The pattern of vault protein mRNA expression is strongly correlated with the expression of other MDR-associated proteins such as MDR1, MRP1 and BCRP. Surprisingly, the protein levels of MVP, TEP1 and vPARP are actually increased in the higher‑grade tumors suggesting existence of post-transcriptional regulation of vault component production.

摘要

穹窿是由三种蛋白质(MVP、TEP1、vPARP)和穹窿相关 RNA(vRNA)组成的细胞质核糖核蛋白颗粒。尽管穹窿的细胞功能仍不清楚,但穹窿与多药耐药(MDR)的发展密切相关,MDR 是有效治疗癌症的主要障碍。现有发表的数据表明,穹窿及其成分在广泛的多药耐药癌细胞系和不同组织来源的肿瘤中经常上调。在这里,我们对未接受化疗的手术后卵巢癌患者样本中的穹窿蛋白表达进行了详细分析。我们的分析表明,穹窿蛋白在健康个体的卵巢中表达,但在癌症患者中的表达发生了变化。具体而言,MVP、TEP1 和 vPARP 的 mRNA 水平在癌症样本中显著降低,且在高级别肿瘤中表达倾向更低。穹窿蛋白 mRNA 表达模式与其他多药耐药相关蛋白(如 MDR1、MRP1 和 BCRP)的表达强烈相关。令人惊讶的是,MVP、TEP1 和 vPARP 的蛋白水平实际上在高级别肿瘤中增加,表明穹窿成分产生存在转录后调控。

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