このエントリーをはてなブックマークに追加
ID 48856
フルテキストURL
著者
Tanimoto, Ryuta Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Sakaguchi, Masakiyo Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Abarzua, Fernando Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kataoka, Ken Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kurose, Kaoru Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Murata, Hitoshi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Nasu, Yasutomo Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kumon, Hiromi Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Huh, Nam-Ho Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
抄録
We have recently shown that an adenovirus carrying REIC/Dkk-3 (Ad-REIC) exhibits a potent tumor-specific cell-killing function for various human cancers. It has also become evident that some human cancers are resistant to Ad-REIC-induced apoptosis. The aim of the present study was to determine the molecular mechanisms of resistance to Ad-REIC. First, we isolated resistant clones from a human prostate cancer cell line, PC3, after repeated exposure to Ad-REIC. Infection efficiency of the adenovirus vector and expression level of REIC/Dkk-3 in the resistant clones were similar to those in the parental PC3 cells. By screening for alteration in levels and functional status of proteins involved in Ad-REIC-induced apoptosis, we found that BiP/GRP78, an ER-residing chaperone protein, was expressed at higher levels consistently among resistant cells. Expression levels of BiP and rates of apoptosis induced by Ad-REIC were inversely correlated. Down-regulation of BiP with siRNA sensitized the resistant cells to Ad-REIC in vivo as well as in culture. These results indicate that BiP is a major determinant of resistance to Ad-REIC-induced apoptosis. Thus BiP is useful for diagnosis of inherent and acquired resistance of cancers and also as a target molecule to overcome resistance to the gene therapeutic Ad-REIC.
キーワード
REIC
Dkk
apoptosis
GRP78
ER stress
発行日
2010-04-01
出版物タイトル
International Journal of Cancer
126巻
7号
開始ページ
1562
終了ページ
1569
ISSN
0020-7136
NCID
AA00680002
資料タイプ
学術雑誌論文
プロジェクト
ナノバイオ標的医療の融合的創出拠点
オフィシャル URL
http://onlinelibrary.wiley.com/doi/10.1002/ijc.24764/abstract
言語
English
著作権者
© 2009 UICC
論文のバージョン
author
査読
有り
DOI
PubMed ID
Web of Sience KeyUT