PMID- 26372254
OWN - NLM
STAT- MEDLINE
DCOM- 20160404
LR  - 20180119
IS  - 1097-0142 (Electronic)
IS  - 0008-543X (Linking)
VI  - 121
IP  - 24
DP  - 2015 Dec 15
TI  - Trefoil factor 1 expression suppresses Helicobacter pylori-induced inflammation
      in gastric carcinogenesis.
PG  - 4348-58
LID - 10.1002/cncr.29644 [doi]
AB  - BACKGROUND: Infection with Helicobacter pylori, a high-risk factor for gastric
      cancer, is frequently associated with chronic inflammation through activation of 
      nuclear factor kappaB (NF-kappaB). Trefoil factor 1 (TFF1) is a constitutively
      expressed protein in the stomach that has tumor-suppressor functions and plays a 
      critical role in maintaining mucosal integrity. This study investigated the role 
      of TFF1 in regulating the proinflammatory response to H. pylori infections.
      METHODS: For in vitro studies, immunofluorescence, luciferase reporter assays,
      Western blots, and quantitative real-time polymerase chain reaction were
      performed to investigate the activation of NF-kappaB and its target genes in
      response to infections with H. pylori strains J166 and 7.13. In addition,
      Tff1-knockout (KO) and Tff1-wild-type mice were used for infections with the H.
      pylori strain called premouse Sydney strain 1. RESULTS: The reconstitution of
      TFF1 expression in gastric cancer cells significantly suppressed H.
      pylori-mediated increases in NF-kappaB-p65 nuclear staining, transcriptional
      activity, and expression of proinflammatory cytokine genes (tumor necrosis factor
      alpha, interleukin 1beta, chemokine [C-X-C motif] ligand 5, and interleukin 4
      receptor) that were associated with reductions in the expression and
      phosphorylation of NF-kappaB-p65 and IkappaB kinase alpha/beta proteins. The in
      vivo studies using the Tff1-KO mouse model of gastric neoplasia confirmed the in 
      vitro findings. Furthermore, they demonstrated increases in chronic inflammation 
      scores and in the frequency of invasive gastric adenocarcinoma in the Tff1-KO
      mice infected with H. pylori versus the uninfected Tff1-KO mice. CONCLUSIONS:
      These findings underscore an important protective role of TFF1 in abrogating H.
      pylori-mediated inflammation, a crucial hallmark of gastric tumorigenesis.
      Therefore, loss of TFF1 expression could be an important step in H.
      pylori-mediated gastric carcinogenesis.
CI  - (c) 2015 American Cancer Society.
FAU - Soutto, Mohammed
AU  - Soutto M
AD  - Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville,
      Tennessee.
AD  - Department of Surgery, Vanderbilt University Medical Center, Nashville,
      Tennessee.
FAU - Chen, Zheng
AU  - Chen Z
AD  - Department of Surgery, Vanderbilt University Medical Center, Nashville,
      Tennessee.
FAU - Katsha, Ahmed M
AU  - Katsha AM
AD  - Department of Surgery, Vanderbilt University Medical Center, Nashville,
      Tennessee.
FAU - Romero-Gallo, Judith
AU  - Romero-Gallo J
AD  - Department of Medicine, Vanderbilt University Medical Center, Nashville,
      Tennessee.
FAU - Krishna, Uma S
AU  - Krishna US
AD  - Department of Medicine, Vanderbilt University Medical Center, Nashville,
      Tennessee.
FAU - Piazuelo, M Blanca
AU  - Piazuelo MB
AD  - Department of Medicine, Vanderbilt University Medical Center, Nashville,
      Tennessee.
FAU - Washington, M Kay
AU  - Washington MK
AD  - Department of Pathology, Vanderbilt University Medical Center, Nashville,
      Tennessee.
FAU - Peek, Richard M Jr
AU  - Peek RM Jr
AD  - Department of Medicine, Vanderbilt University Medical Center, Nashville,
      Tennessee.
AD  - Department of Cancer Biology, Vanderbilt University Medical Center, Nashville,
      Tennessee.
FAU - Belkhiri, Abbes
AU  - Belkhiri A
AD  - Department of Surgery, Vanderbilt University Medical Center, Nashville,
      Tennessee.
FAU - El-Rifai, Wael M
AU  - El-Rifai WM
AD  - Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville,
      Tennessee.
AD  - Department of Surgery, Vanderbilt University Medical Center, Nashville,
      Tennessee.
AD  - Department of Cancer Biology, Vanderbilt University Medical Center, Nashville,
      Tennessee.
LA  - eng
GR  - P01 CA028842/CA/NCI NIH HHS/United States
GR  - P50 CA095103/CA/NCI NIH HHS/United States
GR  - R01 CA077955/CA/NCI NIH HHS/United States
GR  - P50 CA95103/CA/NCI NIH HHS/United States
GR  - P30 CA68485/CA/NCI NIH HHS/United States
GR  - P30 DK058404/DK/NIDDK NIH HHS/United States
GR  - P01 CA116087/CA/NCI NIH HHS/United States
GR  - R01 CA093999/CA/NCI NIH HHS/United States
GR  - P30 CA068485/CA/NCI NIH HHS/United States
GR  - I01 BX001179/BX/BLRD VA/United States
GR  - DK058404/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20150915
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Chemokine CXCL5)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Interleukin-4)
RN  - 0 (Tff1 protein, mouse)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (Trefoil Factor-1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
SB  - AIM
SB  - IM
MH  - Adenocarcinoma/*genetics/immunology/microbiology
MH  - Animals
MH  - Carcinogenesis/*genetics
MH  - Chemokine CXCL5/immunology
MH  - Gastric Mucosa/immunology/*metabolism/microbiology
MH  - Helicobacter Infections/*genetics/immunology
MH  - Helicobacter pylori
MH  - Humans
MH  - I-kappa B Kinase/metabolism
MH  - In Vitro Techniques
MH  - Inflammation
MH  - Interleukin-1beta/immunology
MH  - Mice
MH  - Mice, Knockout
MH  - Peptides/*genetics
MH  - Phosphorylation
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptors, Interleukin-4/immunology
MH  - Stomach/immunology/metabolism/microbiology
MH  - Stomach Neoplasms/*genetics/immunology/microbiology
MH  - Transcription Factor RelA/metabolism
MH  - Trefoil Factor-1
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/immunology
PMC - PMC4670586
MID - NIHMS713494
OTO - NOTNLM
OT  - Helicobacter pylori
OT  - gastric cancer
OT  - inflammation
OT  - nuclear factor kappaB (NF-kappaB)
OT  - trefoil factor 1 (TFF1)
EDAT- 2015/09/16 06:00
MHDA- 2016/04/05 06:00
CRDT- 2015/09/16 06:00
PHST- 2015/04/28 00:00 [received]
PHST- 2015/07/13 00:00 [revised]
PHST- 2015/07/29 00:00 [accepted]
PHST- 2015/09/16 06:00 [entrez]
PHST- 2015/09/16 06:00 [pubmed]
PHST- 2016/04/05 06:00 [medline]
AID - 10.1002/cncr.29644 [doi]
PST - ppublish
SO  - Cancer. 2015 Dec 15;121(24):4348-58. doi: 10.1002/cncr.29644. Epub 2015 Sep 15.