Signaling mediated by the NF-κB sub-units NF-κB1, NF-κB2 and c-Rel differentially regulate Helicobacter felis-induced gastric carcinogenesis in C57BL/6 mice

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Signaling mediated by the NF-κB sub-units NF-κB1, NF-κB2 and c-Rel differentially regulate Helicobacter felis-induced gastric carcinogenesis in C57BL/6 mice. / Burkitt, M D; Williams, J M; Duckworth, C A; O'Hara, A; Hanedi, A; Varro, A; Caamaño, J H; Pritchard, D M.

In: Oncogene, Vol. 32, No. 50, 12.12.2013, p. 5563-73.

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Burkitt, M D ; Williams, J M ; Duckworth, C A ; O'Hara, A ; Hanedi, A ; Varro, A ; Caamaño, J H ; Pritchard, D M. / Signaling mediated by the NF-κB sub-units NF-κB1, NF-κB2 and c-Rel differentially regulate Helicobacter felis-induced gastric carcinogenesis in C57BL/6 mice. In: Oncogene. 2013 ; Vol. 32, No. 50. pp. 5563-73.

Bibtex

@article{c4f3f9bbe3e840b89c525c86dcba85d1,
title = "Signaling mediated by the NF-κB sub-units NF-κB1, NF-κB2 and c-Rel differentially regulate Helicobacter felis-induced gastric carcinogenesis in C57BL/6 mice",
abstract = "The classical nuclear factor-kappaB (NF-κB) signaling pathway has been shown to be important in a number of models of inflammation-associated cancer. In a mouse model of Helicobacter-induced gastric cancer, impairment of classical NF-κB signaling in the gastric epithelium led to the development of increased preneoplastic pathology, however the role of specific NF-κB proteins in Helicobacter-associated gastric cancer development remains poorly understood. To investigate this C57BL/6, Nfkb1(-/-), Nfkb2(-/-) and c-Rel(-/-) mice were infected with Helicobacter felis for 6 weeks or 12 months. Bacterial colonization, gastric atrophy and preneoplastic changes were assessed histologically and cytokine expression was assessed by qPCR. Nfkb1(-/-) mice developed spontaneous gastric atrophy when maintained for 12 months in conventional animal house conditions. They also developed more pronounced gastric atrophy after short-term H. felis colonization with a similar extent of preneoplasia to wild-type (WT) mice after 12 months. c-Rel(-/-) mice developed a similar degree of gastric atrophy to WT mice; 3 of 6 of these animals also developed lymphoproliferative lesions after 12 months of infection. Nfkb2(-/-) mice developed minimal gastric epithelial pathology even 12 months after H. felis infection. These findings demonstrate that NF-κB1- and NF-κB2-mediated signaling pathways differentially regulate the epithelial consequences of H. felis infection in the stomach, while c-Rel-mediated signaling also appears to modulate the risk of lymphomagenesis in gastric mucosa-associated lymphoid tissue. ",
keywords = "Animals, Cell Transformation, Neoplastic/metabolism, Disease Models, Animal, Female, Gastric Mucosa/metabolism, Gene Deletion, Helicobacter Infections/complications, Helicobacter felis, Inflammation/genetics, Mice, Mice, Knockout, NF-kappa B/chemistry, NF-kappa B p50 Subunit/genetics, NF-kappa B p52 Subunit/genetics, Proto-Oncogene Proteins c-rel/metabolism, Signal Transduction, Stomach Neoplasms/etiology",
author = "Burkitt, {M D} and Williams, {J M} and Duckworth, {C A} and A O'Hara and A Hanedi and A Varro and Caama{\~n}o, {J H} and Pritchard, {D M}",
year = "2013",
month = dec,
day = "12",
doi = "10.1038/onc.2013.334",
language = "English",
volume = "32",
pages = "5563--73",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "50",

}

RIS

TY - JOUR

T1 - Signaling mediated by the NF-κB sub-units NF-κB1, NF-κB2 and c-Rel differentially regulate Helicobacter felis-induced gastric carcinogenesis in C57BL/6 mice

AU - Burkitt, M D

AU - Williams, J M

AU - Duckworth, C A

AU - O'Hara, A

AU - Hanedi, A

AU - Varro, A

AU - Caamaño, J H

AU - Pritchard, D M

PY - 2013/12/12

Y1 - 2013/12/12

N2 - The classical nuclear factor-kappaB (NF-κB) signaling pathway has been shown to be important in a number of models of inflammation-associated cancer. In a mouse model of Helicobacter-induced gastric cancer, impairment of classical NF-κB signaling in the gastric epithelium led to the development of increased preneoplastic pathology, however the role of specific NF-κB proteins in Helicobacter-associated gastric cancer development remains poorly understood. To investigate this C57BL/6, Nfkb1(-/-), Nfkb2(-/-) and c-Rel(-/-) mice were infected with Helicobacter felis for 6 weeks or 12 months. Bacterial colonization, gastric atrophy and preneoplastic changes were assessed histologically and cytokine expression was assessed by qPCR. Nfkb1(-/-) mice developed spontaneous gastric atrophy when maintained for 12 months in conventional animal house conditions. They also developed more pronounced gastric atrophy after short-term H. felis colonization with a similar extent of preneoplasia to wild-type (WT) mice after 12 months. c-Rel(-/-) mice developed a similar degree of gastric atrophy to WT mice; 3 of 6 of these animals also developed lymphoproliferative lesions after 12 months of infection. Nfkb2(-/-) mice developed minimal gastric epithelial pathology even 12 months after H. felis infection. These findings demonstrate that NF-κB1- and NF-κB2-mediated signaling pathways differentially regulate the epithelial consequences of H. felis infection in the stomach, while c-Rel-mediated signaling also appears to modulate the risk of lymphomagenesis in gastric mucosa-associated lymphoid tissue.

AB - The classical nuclear factor-kappaB (NF-κB) signaling pathway has been shown to be important in a number of models of inflammation-associated cancer. In a mouse model of Helicobacter-induced gastric cancer, impairment of classical NF-κB signaling in the gastric epithelium led to the development of increased preneoplastic pathology, however the role of specific NF-κB proteins in Helicobacter-associated gastric cancer development remains poorly understood. To investigate this C57BL/6, Nfkb1(-/-), Nfkb2(-/-) and c-Rel(-/-) mice were infected with Helicobacter felis for 6 weeks or 12 months. Bacterial colonization, gastric atrophy and preneoplastic changes were assessed histologically and cytokine expression was assessed by qPCR. Nfkb1(-/-) mice developed spontaneous gastric atrophy when maintained for 12 months in conventional animal house conditions. They also developed more pronounced gastric atrophy after short-term H. felis colonization with a similar extent of preneoplasia to wild-type (WT) mice after 12 months. c-Rel(-/-) mice developed a similar degree of gastric atrophy to WT mice; 3 of 6 of these animals also developed lymphoproliferative lesions after 12 months of infection. Nfkb2(-/-) mice developed minimal gastric epithelial pathology even 12 months after H. felis infection. These findings demonstrate that NF-κB1- and NF-κB2-mediated signaling pathways differentially regulate the epithelial consequences of H. felis infection in the stomach, while c-Rel-mediated signaling also appears to modulate the risk of lymphomagenesis in gastric mucosa-associated lymphoid tissue.

KW - Animals

KW - Cell Transformation, Neoplastic/metabolism

KW - Disease Models, Animal

KW - Female

KW - Gastric Mucosa/metabolism

KW - Gene Deletion

KW - Helicobacter Infections/complications

KW - Helicobacter felis

KW - Inflammation/genetics

KW - Mice

KW - Mice, Knockout

KW - NF-kappa B/chemistry

KW - NF-kappa B p50 Subunit/genetics

KW - NF-kappa B p52 Subunit/genetics

KW - Proto-Oncogene Proteins c-rel/metabolism

KW - Signal Transduction

KW - Stomach Neoplasms/etiology

U2 - 10.1038/onc.2013.334

DO - 10.1038/onc.2013.334

M3 - Article

C2 - 23975431

VL - 32

SP - 5563

EP - 5573

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 50

ER -