Figure 6.
Decreased pSTAT3 levels mediated by AhR KO is associated with the promotion of colon tumorigenesis. WT and intestinal-specific AhR KO (AhRf/f; Villin-Cre) mice were treated with a single dose of AOM (10 mg/kg) by subcutaneous injection, followed by three cycles of 2% DSS for 5 days. Mice were terminated 6 wk after the third cycle of DSS. A: relative Socs3 mRNA expression in uninvolved colonic mucosa, n = 10 mice per group. Immunohistochemistry (B) and quantification (C) of mean fluorescence intensity (MFI) of SOCS3 in uninvolved colonic crypts, n = 4 or 5 mice per group. Immunohistochemistry (D) and quantification (E) of MFI of pSTAT3 in uninvolved colonic crypts, n = 5–7 mice per group. F: relative Reg3b and Reg3g mRNA expression in uninvolved colonic crypts, n = 9 mice per group. G: relative Socs3 mRNA expression in colon tumors from WT and AhR KO mice, n = 3 or 4 mice per group. Immunohistochemistry (H) and quantification (I) of MFI of SOCS3 in colon tumors from WT and AhR KO mice, n = 15–21 fields of view from 2 to 3 mice per group. J: upregulated Socs3 mRNA in colon tumors relative to matched uninvolved mucosa, n = 11 mice. K: quantification of MFI of pSTAT3 between tumor uninvolved and tumor tissues, n = 16–22 fields of view from 5 mice per group. L: decreased Reg3b and Reg3g mRNA expression in colon tumors relative to matched uninvolved mucosa, n = 11 mice. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001. AhR, aryl hydrocarbon receptor; AOM, azoxymethane; DSS, dextran sulfate sodium; KO, knockout; SOCS3, suppressor of cytokine signaling 3; WT, wild type.