Figure 8.

A hypothetical scheme of the role of AhR and AhRR in breast cancer development. AhR agonists like kynurenine (Kyn) are produced in the tumor microenvironment and activate AhR in cells of the tumor microenvironment including stromal and inflammatory cells or the tumor cells themselves. Activation of the PKA pathway and the increased expression of inflammatory mediators such as C/EBPβ and COX-2 contribute to mammary cell transformation and increased cell proliferation. The activated AhR pathway can also induce the activity of the immune-regulatory enzymes IDO and TDO, which metabolize tryptophan into the endogenous AhR ligand Kyn in a positive feedback loop. AhRR may function as an inhibitor of the tumor promoting mechanisms triggered by AhR in the tumor microenvironment. IDO, indoleamine 2,3-dioxygenase; TDO, tryptophan-2,3-dioxygenase; PKA, protein kinase A; Kyn, kynurenine.