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      1. Author :
        Sakaguchi, Masakiyo; Kataoka, Ken; Abarzua, Fernando; Tanimoto, Ryuta; Watanabe, Masami; Murata, Hitoshi; Than, Swe Swe; Kurose, Kaoru; Kashiwakura, Yuji; Ochiai, Kazuhiko; Nasu, Yasutomo; Kumon, Hiromi; Huh, Nam-ho
      2. Title :
      3. Type :
        Journal Article
      4. Year :
      5. Publication :
        The Journal of biological chemistry
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      10. Research Area :
      11. Keywords :
        Adenoviridae; Animals; Bioware; Cell Line, Tumor; Cell Proliferation; Endoplasmic Reticulum; Fibroblasts; Humans; Intercellular Signaling Peptides and Proteins; Interferon Regulatory Factor-1; Interleukin-7; MAP Kinase Kinase Kinase 5; Mice; Neoplasms; p38 Mitogen-Activated Protein Kinases; PC-3M-luc; Signal Transduction; STAT1 Transcription Factor
      12. 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 IRE1alpha, 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.
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      14. Call Number :
        PKI @ catherine.lautenschlager @
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