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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
ATP Binding Cassette Transporter, Subfamily B
-
ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis
-
ATP Binding Cassette Transporter, Subfamily G, Member 2
-
ATP-Binding Cassette Transporters / biosynthesis
-
Carrier Proteins / genetics*
-
Drug Resistance, Multiple*
-
Drug Resistance, Neoplasm*
-
Female
-
Gene Expression Profiling
-
Gene Expression Regulation, Neoplastic*
-
Humans
-
Multidrug Resistance-Associated Proteins / biosynthesis
-
Neoplasm Proteins / biosynthesis
-
Ovarian Neoplasms / metabolism*
-
Ovarian Neoplasms / surgery
-
Poly(ADP-ribose) Polymerases / genetics*
-
RNA, Messenger / biosynthesis
-
RNA-Binding Proteins
-
Tumor Cells, Cultured
-
Up-Regulation
-
Vault Ribonucleoprotein Particles / genetics*
Substances
-
ABCB1 protein, human
-
ABCG2 protein, human
-
ATP Binding Cassette Transporter, Subfamily B
-
ATP Binding Cassette Transporter, Subfamily B, Member 1
-
ATP Binding Cassette Transporter, Subfamily G, Member 2
-
ATP-Binding Cassette Transporters
-
Carrier Proteins
-
Multidrug Resistance-Associated Proteins
-
Neoplasm Proteins
-
RNA, Messenger
-
RNA-Binding Proteins
-
TEP1 protein, human
-
Vault Ribonucleoprotein Particles
-
major vault protein
-
Poly(ADP-ribose) Polymerases
-
vault poly(ADP-ribose) polymerase
-
multidrug resistance-associated protein 1