Helicobacter infection is required for inflammation and colon cancer in Smad3-deficient mice

Maggio-Price, Lillian, Treuting, Piper, Zeng, Weiping, Tsang, Mark, Bielefeldt - Ohmann, Helle and Iritani, Brian M. (2006) Helicobacter infection is required for inflammation and colon cancer in Smad3-deficient mice. Cancer Research, 66 2: 828-838. doi:10.1158/0008-5472.CAN-05-2448

Author Maggio-Price, Lillian
Treuting, Piper
Zeng, Weiping
Tsang, Mark
Bielefeldt - Ohmann, Helle
Iritani, Brian M.
Title Helicobacter infection is required for inflammation and colon cancer in Smad3-deficient mice
Journal name Cancer Research   Check publisher's open access policy
ISSN 0008-5472
Publication date 2006-01
Sub-type Article (original research)
DOI 10.1158/0008-5472.CAN-05-2448
Volume 66
Issue 2
Start page 828
End page 838
Total pages 11
Place of publication Philadelphia, PA, U.S.A.
Publisher American Association for Cancer Research
Language eng
Subject 07 Agricultural and Veterinary Sciences
0707 Veterinary Sciences
0702 Animal Production
Abstract Accumulating evidence suggests that intestinal microbial organisms may play an important role in triggering and sustaining inflammation in individuals afflicted with inflammatory bowel disease (IBD). Moreover, individuals with IBD are at increased risk for developing colorectal cancer, suggesting that chronic inflammation may initiate genetic or epigenetic changes associated with cancer development. We tested the hypothesis that bacteria may contribute to the development of colon cancer by synergizing with defective transforming growth factor-β (TGF-β) signaling, a pathway commonly mutated in human colon cancer. Although others have reported that mice deficient in the TGF-β signaling molecule SMAD3 develop colon cancer, we found that SMAD3-deficient mice maintained free of the Gram-negative enterohepatic bacteria Helicobacter spp. for up to 9 months do not develop colon cancer. Furthermore, infection of SMAD3-/- mice with Helicobacter triggers colon cancer in 50% to 66% of the animals. Using real-time PCR, we found that Helicobacter organisms concentrate in the cecum, the preferred site of tumor development. Mucinous adenocarcinomas develop 5 to 30 weeks after infection and are preceded by an early inflammatory phase, consisting of increased proliferation of epithelial cells; increased numbers of cyclooxygenase-2-positive cells, CD4+ T cells, macrophages; and increased MHC class II expression. Colonic tissue revealed increased transcripts for the oncogene c-myc and the proinflammatory cytokines interleukin-1α (IL-1α), IL-1β, IL-6, IFN-γ, and tumor necrosis factor-α, some of which have been implicated in colon cancer. These results suggest that bacteria may be important in triggering colorectal cancer, notably in the context of gene mutations in the TGF-β signaling pathway, one of the most commonly affected cellular pathways in colorectal cancer in humans.
Keyword Intestinal bacteria
Inflammatory Bowel Disease
Colorectal Cancer
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Veterinary Science Publications
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Created: Mon, 07 Dec 2009, 10:05:03 EST by Rosalind Blair on behalf of Faculty Of Nat Resources, Agric & Veterinary Sc