Expression and activity of aryl hydrocarbon receptors in development and cancer

Although the aryl hydrocarbon receptor (AhR) has been known as the mediator of the toxicity of particular xenobiotics such as the dioxins, the normal role of this transcription factor in a number of biological processes is just beginning to be recognized. Knowledge of AhR-targeted genes and signaling pathways indicates involvement of AhR in fundamental cell-regulatory pathways. Noted defects in the morphology and functions of certain tissues in the absence of AhR point to critical roles for this protein in developmental processes. Together, the data suggest that the AhR has an important function in controlling the balance among processes involved in cell proliferation, death, and differentiation rather than being essential for them. On the other hand, deregulation of these processes is known to contribute to events such as tumor initiation, promotion, and progression that ultimately lead to malignant tumor formation. Epidemiological and experimental animal data, along with a more detailed understanding of how AhR is involved in regulating particular signaling pathways, provide substantial support for an association between abnormal AhR function and cancer. Here we describe the current understanding of how the AhR may function to regulate both normal and cancerous tissue growth and development.