2007年7月
Heat shock proteins play a crucial role in tumor-specific apoptosis by REIC/Dkk-3
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
- 巻
- 20
- 号
- 1
- 開始ページ
- 37
- 終了ページ
- 43
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- 出版者・発行元
- PROFESSOR D A SPANDIDOS
We recently showed that overexpression of REIC/Dickkopf-3 (Dkk-3), a tumor suppressor gene, induced apoptosis in a tumor cell-specific manner. The aim of the present study was to determine the mechanisms underlying the selective induction of apoptosis. At first, we found a mouse renal carcinoma cell line, RENCA, to be extremely sensitive to an adenovirus carrying REIC/Dkk-3 (Ad-REIC), and we showed that activation of c-Jun N-terminal kinase (JNK) was a critical step in cell death, i.e. a process similar to that in human prostate and testicular cancer observed in our previous studies. Among the proteins interfering with the activation of JNK, heat shock protein (Hsp)70/72 was reduced in expression in RENCA cells compared with that in NIH3T3 cells. An Hsp70/72 inducer protected RENCA cells from Ad-REIC-induced apoptosis, while an Hsp70/72 inhibitor sensitized NIH3T3 cells for apoptosis induction. These results indicate that functionally active Hsp70/72 is a key factor in tumor cell-specific induction of apoptotic cell death and that analyses of the expression levels of Hsp70/72 may be essential in determining the significance of Ad-REIC-based gene therapy against human cancer.
- リンク情報
- ID情報
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- ISSN : 1107-3756
- Web of Science ID : WOS:000247492900005