0 146

Cited 0 times in

Direct activation of the human major vault protein gene by DNA-damaging agents

 Yuichi Shimamoto  ;  Tomoyuki Sumizawa  ;  Misako Haraguchi  ;  Takenari Gotanda  ;  Hei-Cheul Jueng  ;  Tatsuhiko Furukawa  ;  Ryuzo Sakata  ;  Shin-Ichi Akiyama 
 ONCOLOGY REPORTS, Vol.15(3) : 645-652, 2006 
Journal Title
Issue Date
Antineoplastic Agents/pharmacology* ; Binding Sites/genetics ; Butyrates/pharmacology ; Camptothecin/analogs & derivatives ; Camptothecin/pharmacology ; Cell Line, Tumor ; Cell Survival/drug effects ; Cisplatin/pharmacology ; Dose-Response Relationship, Drug ; Doxorubicin/pharmacology ; Etoposide/pharmacology ; Gene Expression Regulation, Neoplastic/drug effects* ; Humans ; Immunoblotting ; Irinotecan ; Luciferases/genetics ; Luciferases/metabolism ; Promoter Regions, Genetic/genetics ; RNA Stability/drug effects ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Recombinant Fusion Proteins/genetics ; Recombinant Fusion Proteins/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transfection ; Vault Ribonucleoprotein Particles/genetics* ; Vault Ribonucleoprotein Particles/metabolism
major vault protein/lung resistance-related protein ; multidrug resistance ; anticancer agent ; DNA damage ; gene expression
Vaults are barrel-shaped cytoplasmic ribonucleoprotein particles composed of three proteins. One of the components, the major vault protein (MVP) initially named the lung resistance-related protein (LRP), was found to be overexpressed in various multidrug resistant cancer cell lines and clinical samples. In this study, we investigated whether anticancer drugs could directly induce MVP protein or gene expression in the SW-620 human colorectal cancer cell line, in which MVP has been shown to be induced by the differentiation-inducing agent, sodium butyrate (NaB). MVP protein levels were enhanced in SW-620 cells after a 72 h treatment with doxorubicin (Adr), etoposide (VP-16), cis-platinum (II) diammine dichloride (CDDP) or SN-38, but not vincristine (VCR) or paclitaxel (Taxol) at their IC50 concentration. Treatment for 48 h with Adr, VP-16 and SN-38 at their IC50 concentration also enhanced the expression of MVP mRNA. Moreover, Adr could directly enhance the transcriptional activity of MVP promoter regions. On the other hand, the Adr treatment did not affect the stability of MVP mRNA. Furthermore, MVP levels were also elevated after treatment with the DNA-damaging agents, ethidium bromide (EtBr) and ultraviolet light (UV) irradiation. Our findings therefore suggest that DNA damage enhances MVP promoter activity. Since the MVP protein and mRNA have low turnover rates, a slight enhancement of MVP promoter activity could lead to a considerable increase in the level of MVP.
Full Text
Appears in Collections:
5. Research Institutes (연구소) > Cancer Metastasis Research Center (암전이연구센터) > 1. Journal Papers
Yonsei Authors
Jeung, Hei Cheul(정희철) ORCID logo https://orcid.org/0000-0003-0952-3679
사서에게 알리기


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.