May, 2009
Overexpression of REIC/Dkk-3 in Normal Fibroblasts Suppresses Tumor Growth via Induction of Interleukin-7
JOURNAL OF BIOLOGICAL CHEMISTRY
- Volume
- 284
- Number
- 21
- First page
- 14236
- Last page
- 14244
- Language
- English
- Publishing type
- Research paper (scientific journal)
- DOI
- 10.1074/jbc.M808002200
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
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.
- Link information
-
- DOI
- https://doi.org/10.1074/jbc.M808002200
- CiNii Articles
- http://ci.nii.ac.jp/naid/80020345833
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/19279003
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000266286100030&DestApp=WOS_CPL
- URL
- http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=67649827862&origin=inward
- ID information
-
- DOI : 10.1074/jbc.M808002200
- ISSN : 0021-9258
- CiNii Articles ID : 80020345833
- Pubmed ID : 19279003
- SCOPUS ID : 67649827862
- Web of Science ID : WOS:000266286100030