ArticleThe American journal of pathology2009
Bacterial infection of Smad3/Rag2 double-null mice with transforming growth factor-beta dysregulation as a model for studying inflammation-associated colon cancer.
Article in The American journal of pathology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Comparative study and meta-analysis of meta-analysis studies for the correlation of genomic markers with early cancer detection.Human genomics · 2013Pooled it
- Effect of Chronic Vitamin D Deficiency on the Development and Severity of DSS-Induced Colon Cancer inComparative medicine · 2020Article
- TGF-β in inflammatory bowel disease: a key regulator of immune cells, epithelium, and the intestinal microbiota.Journal of gastroenterology · 2017Review
- Smad3 promotes cancer progression by inhibiting E4BP4-mediated NK cell development.Nature communications · 2017Article
- Helicobacter bilis Infection Alters Mucosal Bacteria and Modulates Colitis Development in Defined Microbiota Mice.Inflammatory bowel diseases · 2016Article
- Lamellipodin-Deficient Mice: A Model of Rectal Carcinoma.PloS one · 2016Article
- Helicobacter cinaedi induced typhlocolitis in Rag-2-deficient mice.Helicobacter · 2015Article
- Interactions between Myc and Mediators of Inflammation in Chronic Liver Diseases.Mediators of inflammation · 2015Review
- Microbiota disbiosis is associated with colorectal cancer.Frontiers in microbiology · 2015Article
- Increased dietary vitamin D suppresses MAPK signaling, colitis, and colon cancer.Cancer research · 2014Article
- Isolation of Helicobacter spp. from mice with rectal prolapses.Comparative medicine · 2014Article
- Colitis and colon cancer in WASP-deficient mice require helicobacter species.Inflammatory bowel diseases · 2013Article
- Characterization of dextran sodium sulfate-induced inflammation and colonic tumorigenesis in Smad3(-/-) mice with dysregulated TGFβ.PloS one · 2013Article
- Macrophages promote fibroblast growth factor receptor-driven tumor cell migration and invasion in a CXCR2-dependent manner.Molecular cancer research : MCR · 2012Article
- A bacterial driver-passenger model for colorectal cancer: beyond the usual suspects.Nature reviews. Microbiology · 2012Review
- 4-hydroxy-2-nonenal mediates genotoxicity and bystander effects caused by Enterococcus faecalis-infected macrophages.Gastroenterology · 2012Article
- Lack of effect of murine norovirus infection on a mouse model of bacteria-induced colon cancer.Comparative medicine · 2011Article
- Towards the human colorectal cancer microbiome.PloS one · 2011Article
- Persistent infection of rhesus monkeys with 'Helicobacter macacae' and its isolation from an animal with intestinal adenocarcinoma.Journal of medical microbiology · 2010Article
- P58(IPK): a novel "CIHD" member of the host innate defense response against pathogenic virus infection.PLoS pathogens · 2009Article
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Alterations in genes encoding transforming growth factor-beta-signaling components contribute to colon cancer in humans. Similarly, mice deficient in the transforming growth factor-beta signaling molecule, Smad3, develop colon cancer, but only after a bacterial trigger occurs, resulting in chronic inflammation. To determine whether Smad3-null lymphocytes contribute to increased cancer susceptibility, we crossed Smad3-null mice with mice deficient in both B and T lymphocytes (Rag2(-/-) mice). Helicobacter-infected Smad3/Rag2-double knockout (DKO) mice had more diffuse inflammation and increased incidence of adenocarcinoma compared with Helicobacter-infected Smad3(-/-) or Rag2(-/-) mice alone. Adoptive transfer of WT CD4(+)CD25(+) T-regulatory cells provided significant protection of Smad3/Rag2-DKO from bacterial-induced typhlocolitis, dysplasia, and tumor development, whereas Smad3(-/-) T-regulatory cells provided no protection. Immunohistochemistry, real-time reverse transcriptase-polymerase chain reaction, and Western blot analyses of colonic tissues from Smad3/Rag2-DKO mice 1 week after Helicobacter infection revealed an influx of macrophages, enhanced nuclear factor-kappaB activation, increased Bcl(XL)/Bcl-2 expression, increased c-Myc expression, accentuated epithelial cell proliferation, and up-regulated IFN-gamma, IL-1alpha, TNF-alpha, IL-1beta, and IL-6 transcription levels. These results suggest that the loss of Smad3 increases susceptibility to colon cancer by at least two mechanisms: deficient T-regulatory cell function, which leads to excessive inflammation after a bacterial trigger; and increased expression of proinflammatory cytokines, enhanced nuclear factor-kappaB activation, and increased expression of both pro-oncogenic and anti-apoptotic proteins that result in increased cell proliferation/survival of epithelial cells in colonic tissues.
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