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ID 48854
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Author
Kataoka, Ken
Abarzua, Fernando
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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True
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