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ID 48856
FullText URL
Author
Tanimoto, Ryuta Kaken ID
Abarzua, Fernando
Kataoka, Ken
Kurose, Kaoru
Abstract
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.
Keywords
REIC
Dkk
apoptosis
GRP78
ER stress
Published Date
2010-04-01
Publication Title
International Journal of Cancer
Volume
volume126
Issue
issue7
Start Page
1562
End Page
1569
ISSN
0020-7136
NCID
AA00680002
Content Type
Journal Article
Project
Innovation Center Okayama for Nanobio-targeted Therapy(ICONT)
Official Url
http://onlinelibrary.wiley.com/doi/10.1002/ijc.24764/abstract
language
英語
Copyright Holders
© 2009 UICC
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Refereed
True
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