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Aromatic Hydrocarbon Receptor Down‐regulates MYCN Expression and Promotes Neural Differentiation of Neuroblastoma

Neuroblastoma (NB) is a heterogeneous neoplasm derived from sympathoadreanal lineage of the neural crest progenitor cells, and is the most common malignant disease of infancy. MYCN amplification is a prognostic factor of NB. It indicates a highly malignant disease and poor patient prognosis. However, how MYCN affects the NB cell behavior remains unclear. By DNA arrays and pathway analysis, aromatic hydrocarbon receptor (AHR) was found to reversely correlate with the MYCN expression in NB tumors. In addition, positive AHR expression by immunostaining of NB tumors predicted a favorable prognosis. AHR was known as the mediator of the toxicity of dioxin‐like compounds. However, recent studies demonstrated that AHR is important in regulating cell death, proliferation, and differentiation. We hypothesize that AHR could regulate MYCN expression in NB. Over‐expressed AHR promotes SK‐N‐DZ cell neuronal differentiation and down‐regulate the mRNA expression of MYCN. Our results suggested that AHR not only relates to the MYCN expression but also plays an important role in regulating tumorigenesis of NB.