title: Effects of growth arrest and DNA damage-inducible protein 34 (GADD34) on inflammation-induced colon cancer in mice.
abstract: BACKGROUND
  Growth arrest and DNA damage-inducible protein 34 (GADD34/Ppp1r15a) is a family of GADD proteins that are induced by DNA damage. GADD34 protein has been suggested to regulate inflammation or host defense systems. However, the in vivo function of GADD34 in inflammation is still unclear. Long lasting inflammation, such as that seen in Crohn's disease and ulcerative colitis, is associated with a higher incidence of colorectal cancer (CRC).
  
  
  METHODS
  Using a colitis-associated cancer model, we analysed GADD34-deficient (KO) mice to study the effect of GADD34 on colitis and colorectal tumorigenesis.
  
  
  RESULTS
  We found a higher incidence of CRC in wild-type (WT) mice than in GADD34KO mice. Moreover, dextran sodium sulfate (DSS)-induced inflammatory responses were downregulated by GADD34 deficiency. The expression of pro-inflammatory mediators such as TNFα, IL-6, and iNOS/NOS2 was higher in the colons of WT mice than GADD34KO mice. IL-6 is known to activate STAT3 signalling in colonic epithelial cells and subsequently induced epithelial proliferation. We found that IL-6-STAT3 signalling and epithelial proliferation were higher in WT mice compared with GADD34KO mice.
  
  
  CONCLUSIONS
  These results indicated that GADD34 upregulated pro-inflammatory mediator production leading to a higher tumour burden following azoxymethane (AOM)/DSS treatment.
authors.affiliation: Department of Immunology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Immunology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Immunology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
authors.forename: Reina
authors.initials: R
authors.lastname: Oshino
authors.affiliation: Department of Immunology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
authors.forename: Nana
authors.initials: N
authors.lastname: Chen
authors.affiliation: Department of Immunology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Nishio
authors.affiliation: Department of Immunology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Isobe
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D003092:Colitis / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D004249:DNA Damage / Q000502:physiology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D054645:Protein Phosphatase 1 / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
chemical_list: D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; C513256:Ppp1r15a protein, mouse; D054645:Protein Phosphatase 1