Cecal tumorigenesis in AhR-deficient mice depends on cecum-specific MAPK pathway activation and inflammation.

Cecal tumorigenesis in AhR-deficient mice depends on cecum-specific MAPK pathway activation and inflammation. Am J Pathol. 2019 Nov 14;: Authors: Matoba H, Takamoto M, Fujii C, Kawakubo M, Kasuga E, Matsumura T, Natori T, Misawa K, Taniguchi S, Nakayama J Abstract The aryl hydrocarbon receptor (AhR) is a transcription factor known as a dioxin receptor. Recently, Ahr-/- mice were revealed to develop cecal tumors with inflammation and Wnt/β-catenin pathway activation. However, whether β-catenin degradation is AhR-dependent remains unclear. To determine whether other signaling pathways function in Ahr-/- cecal tumorigenesis, we investigated histological characteristics of the tumors, cytokine/chemokine production in tumors and Ahr-/- peritoneal macrophages. AhR expression was also assessed in human colorectal carcinomas. Ten of the 28 Ahr-/- mice developed cecal lesions by 50 weeks of age, an incidence significantly lower than previously reported. Cecal lesions of Ahr-/- mice developed from serrated hyperplasia to adenoma/dysplasia-like neoplasia with enhanced proliferation. Macrophage and neutrophil infiltration into the lesions was also observed early in serrated hyperplasia, although adjacent mucosa was devoid of inflammation. Il1b, Il6, Ccl2, and Cxcl5 were up-regulated at lesion sites, while only IL-6 production increased in Ahr-/- peritoneal macrophages following LPS+ATP stimulation. Neither c-Myc up-regulation nor β-catenin nu...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research