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ID 30945
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Author
Kobayashi, Tomoko
Tanimoto, Ryuta
Abarzua, Fernando
Takaishi, Mikiro
Saika, Takashi
Miyazaki, Masahiro
Huh, Nam-ho
Abstract

We have recently shown that a new therapeutic modality using the REIC/Dkk-3 gene (Ad-REIC) is effective against various human cancers, including those of prostate, testis and breast origins. The aim of the present study was to examine the sensitivity of bladder cancers to Ad-REIC and to clarify the molecular mechanisms that determine sensitivity/resistance. We found that 2 human bladder cancer cell lines, T24 and J82, are resistant to Ad-REIC. In T24 and J82 cells, the ER stress response and activation of JNK were observed in a manner similar to that in the sensitive PC3 cells. Translocation of Bax to mitochondria occurred in PC3 cells but not in T24 and J82 cells. Bcl-2 was remarkably overexpressed in T24 and J82 compared with the expression levels in sensitive cell lines. Treatment of T24 and J82 cells with a Bcl-2 inhibitor sensitized the cells to Ad-REIC-induced apoptosis. The results indicate that some human bladder cancers are resistant to apoptosis induced by overexpression of REIC/Dkk-3, which is at least in part due to up-regulation of Bcl-2. These results provide a basis for possible use of Bcl-2 as a marker of sensitive cancers and to try to sensitize resistant cancers to Ad-REIC by down-regulation of Bcl-2.

Keywords
REIC/Dkk-3
bladder cancer
apoptosis
Bcl-2
Amo Type
Original Article
Published Date
2008-12
Publication Title
Acta Medica Okayama
Volume
volume62
Issue
issue6
Publisher
Okayama University Medical School
Start Page
393
End Page
401
ISSN
0386-300X
NCID
AA00508441
Content Type
Journal Article
language
英語
File Version
publisher
Refereed
True
Web of Sience KeyUT