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ID 48854
FullText URL
Author
Kataoka, Ken
Abarzua, Fernando
Tanimoto, Ryuta Kaken ID
Than, Swe Swe
Kurose, Kaoru
Kashiwakura, Yuji
Ochiai, Kazuhiko
Abstract
We previously showed that the tumor suppressor gene REIC/Dkk-3, when overexpressed by an adenovirus (Ad-REIC), exhibited a dramatic therapeutic effect on human cancers through a mechanism triggered by endoplasmic reticulum stress. Adenovirus vectors show no target cell specificity and thus may elicit unfavorable side effects through infection of normal cells even upon intra-tumoral injection. In this study, we examined possible effects of Ad-REIC on normal cells. We found that infection of normal human fibroblasts (NHF) did not cause apoptosis but induced production of interleukin (IL)-7. The induction was triggered by endoplasmic reticulum stress and mediated through IRE1 alpha, ASK1, p38, and IRF-1. When Ad-REIC-infected NHF were transplanted in a mixture with untreated human prostate cancer cells, the growth of the cancer cells was significantly suppressed. Injection of an IL-7 antibody partially abrogated the suppressive effect of Ad-REIC-infected NHF. These results indicate that Ad-REIC has another arm against human cancer, an indirect host-mediated effect because of overproduction of IL-7 by mis-targeted NHF, in addition to its direct effect on cancer cells.
Published Date
2009-05-22
Publication Title
The Journal of Biological Chemistry
Volume
volume284
Issue
issue21
Publisher
The American Society for Biochemistry and Molecular Biology, Inc.
Start Page
14236
End Page
14244
ISSN
0021-9258
NCID
AA00251083
Content Type
Journal Article
Project
Innovation Center Okayama for Nanobio-targeted Therapy(ICONT)
Official Url
http://www.jbc.org/content/284/21/14236.long
language
英語
Copyright Holders
© 2009 by The American Society for Biochemistry and Molecular Biology, Inc.
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