ID | 30945 |
JaLCDOI | |
FullText URL | |
Author |
Kobayashi, Tomoko
Tanimoto, Ryuta
Abarzua, Fernando
Takaishi, Mikiro
Kataoka, Ken
Kaken ID
researchmap
Saika, Takashi
Miyazaki, Masahiro
Huh, Nam-ho
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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
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Amo Type | Original Article
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Publication Title |
Acta Medica Okayama
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Published Date | 2008-12
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Volume | volume62
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Issue | issue6
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Publisher | Okayama University Medical School
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Start Page | 393
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End Page | 401
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ISSN | 0386-300X
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NCID | AA00508441
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Content Type |
Journal Article
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language |
English
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File Version | publisher
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Refereed |
True
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Web of Science KeyUT |