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
Kaken ID
Sakaguchi, Masakiyo
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
ORCID
Kaken ID
publons
researchmap
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
Kaken ID
publons
researchmap
Nasu, Yasutomo
Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kaken ID
publons
researchmap
Kumon, Hiromi
Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kaken ID
publons
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
|
巻 | 126巻
|
号 | 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 |
英語
|
著作権者 | © 2009 UICC
|
論文のバージョン | author
|
査読 |
有り
|
DOI | |
PubMed ID | |
Web of Science KeyUT |