| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2008 |
| Předmět: |
|
| Zdroj: |
Acta Medica Okayama. 62(6):393-401 |
| ISSN: |
0386-300X |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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