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Updated: Jun 20, 2026
Modeling Colitis-Associated Cancer with Azoxymethane (AOM) and Dextran Sulfate Sodium (DSS)
Published on: September 11, 2012
Pla2g2a attenuates colon tumorigenesis in azoxymethane-treated C57BL/6 mice; expression studies reveal Pla2g2a target
Remond J A Fijneman1, Lindsey K Bade, Johannes R Peham
1Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
Background:
The group IIA secretory phospholipase A2 gene, Pla2g2a, confers resistance to intestinal tumorigenesis in the Apc(Min/+) mouse model. However, it is unclear how Pla2g2a exerts its tumor-suppressive effects and whether its mode of action depends on Apc-germline mutations.
Methods:
We tested whether expression of a Pla2g2a transgene provides protection against carcinogen-induced colon tumors, and examined whether the normal colon microenvironment is modulated by Pla2g2a expression.
Results:
Pla2g2a strongly inhibited colon tumorigenesis in mice following treatment with the DNA alkylating agent azoxymethane (AOM). Moreover, AOM-induced duodenal tumors were also attenuated by Pla2g2a expression. These tumors demonstrated upregulation of beta-catenin, indicative of involvement of the Wnt signaling pathway. Comparison of genome-wide microarray expression profiles of healthy (non-pathologic) colon tissues from Pla2g2a-transgenic to non-transgenic mice revealed 382 genes that were differentially expressed, comprising clusters of genes involved in inflammation and microbial defense, cell signaling and cell cycle, transactivation, apoptosis and mitochondrial function, DNA repair, and lipid and energy metabolism. Pathway analysis using Gene Set Enrichment Analysis (GSEA) indicated that Pla2g2a suppresses the expression of interferon-induced genes.
Conclusion:
Our results demonstrate that Pla2g2a attenuates colon tumorigenesis independent of Apc-germline mutations, and reveal Pla2g2a target genes and pathways in non-pathologic colon microenvironment that influence conditions for colorectal cancer development.
Insights
Group IIA secretory phospholipase A2 (Pla2g2a) gene inhibits intestinal cancer in mice. Pla2g2a suppresses colon tumorigenesis independently of Apc mutations by modulating the colon microenvironment.
Area of Science:
- Gastroenterology
- Oncology
- Molecular Biology
Background:
- The group IIA secretory phospholipase A2 (Pla2g2a) gene is known to confer resistance to intestinal tumorigenesis in the Apc(Min/+) mouse model.
- The precise mechanisms by which Pla2g2a exerts its tumor-suppressive effects and its dependence on Apc-germline mutations remain unclear.
Purpose of the Study:
- To investigate whether Pla2g2a transgene expression protects against carcinogen-induced colon tumors.
- To examine the modulation of the normal colon microenvironment by Pla2g2a expression.
Main Methods:
- Testing the protective effects of a Pla2g2a transgene against azoxymethane (AOM)-induced colon tumorigenesis in mice.
- Analyzing AOM-induced duodenal tumors for beta-catenin upregulation.
- Comparing genome-wide microarray expression profiles of healthy colon tissues from Pla2g2a-transgenic and non-transgenic mice.
- Performing pathway analysis using Gene Set Enrichment Analysis (GSEA).
Main Results:
- Pla2g2a significantly inhibited colon and duodenal tumorigenesis induced by AOM.
- AOM-induced tumors showed beta-catenin upregulation, suggesting Wnt signaling pathway involvement.
- Microarray analysis revealed 382 differentially expressed genes in healthy colon tissue, including those involved in inflammation, microbial defense, cell signaling, apoptosis, DNA repair, and metabolism.
- GSEA indicated that Pla2g2a suppresses the expression of interferon-induced genes.
Conclusions:
- Pla2g2a attenuates colon tumorigenesis independently of Apc-germline mutations.
- The study identified Pla2g2a target genes and pathways within the non-pathologic colon microenvironment that influence colorectal cancer development.
