Papers

May, 2009

Overexpression of REIC/Dkk-3 in Normal Fibroblasts Suppresses Tumor Growth via Induction of Interleukin-7

JOURNAL OF BIOLOGICAL CHEMISTRY
  • Masakiyo Sakaguchi
  • Ken Kataoka
  • Fernando Abarzua
  • Ryuta Tanimoto
  • Masami Watanabe
  • Hitoshi Murata
  • Swe Swe Than
  • Kaoru Kurose
  • Yuji Kashiwakura
  • Kazuhiko Ochiai
  • Yasutomo Nasu
  • Hiromi Kumon
  • Nam-ho Huh
  • Display all

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

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