JaLCDOI | 10.18926/AMO/30945 |
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FullText URL | fulltext.pdf |
Author | Kobayashi, Tomoko| Sakaguchi, Masakiyo| Tanimoto, Ryuta| Abarzua, Fernando| Takaishi, Mikiro| Kaku, Haruki| Kataoka, Ken| Saika, Takashi| Nasu, Yasutomo| Miyazaki, Masahiro| Kumon, Hiromi| 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 |
Publication Title | Acta Medica Okayama |
Published Date | 2008-12 |
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 | English |
File Version | publisher |
Refereed | True |
Web of Science KeyUT | 000262025000006 |