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Conclusion Exposure to TCDD induces a mechanism of two-stage regulation of the expression of some IL-12 family subunits through primary activation of the aryl hydrocarbon receptor by the TCDD-containing complex followed by ATF3-dependent suppression of their expression. This may result in an abrupt reduction of the anti-tumor response mediated by O and NK cells. The observed increase in ATF3 and decrease in IL-12 following exposure to TCDD are consistent with data on the expression of these genes in tumor-associated macrophages (TAMs). Reliance upon available data that demonstrate a decrease in IL-12 alongside an increase in the expression of other cytokines typical of TAMs confirms the hypothesis that TCDD can shift the phenotype of a macrophage towards a tumor-associated direction. This mechanism may be one of the others underlying TCDD-driven tumor promotion. This work was supported by the Russian Foundation for Basic Research(Russia) (No. 12-04-01736) and state projects VI.60.1.1 and VI.61.1.2.
Source: European Journal of Cancer Supplements - Category: Cancer & Oncology Source Type: research