title: A role for the aryl hydrocarbon receptor in mammary gland tumorigenesis.
abstract: The aryl hydrocarbon receptor (AhR) is an evolutionarily conserved transcription factor bound and activated by ubiquitous environmental pollutants. Historically, the AhR has been studied for its transcriptional regulation of genes encoding cytochrome P450 enzymes, which metabolize many of these chemicals into mutagenic and toxic intermediates. However, recent studies demonstrate that the AhR plays an important role in the biology of several cell types in the absence of environmental chemicals. Here, this paradigm shift is discussed in the context of a putative role for the AhR in mammary gland tumorigenesis. Data demonstrating high levels of constitutively active AhR in mammary tumors are summarized. Particular focus is placed on the likelihood that the AhR contributes to ongoing mammary tumor cell growth and on the possibility that the AhR inhibits apoptosis while promoting transition to an invasive, metastatic phenotype. A working model is proposed that may help explain the sometimes contradictory outcomes observed after AhR manipulation and that serves as a blueprint for the design of therapeutics which target the AhR in breast cancer. The theme that malignant cells reveal the functions for which the AhR has been evolutionarily conserved is presented throughout this discussion.
authors.affiliation: Department of Environmental Health, Boston University School of Public Health, Boston, MA 02118, USA.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Schlezinger
authors.forename: Donghui
authors.initials: D
authors.lastname: Liu
authors.forename: Marganit
authors.initials: M
authors.lastname: Farago
authors.forename: David C
authors.initials: DC
authors.lastname: Seldin
authors.forename: Karine
authors.initials: K
authors.lastname: Belguise
authors.forename: Gail E
authors.initials: GE
authors.lastname: Sonenshein
authors.forename: David H
authors.initials: DH
authors.lastname: Sherr
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000235:genetics* / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics* / Q000378:metabolism
chemical_list: D002273:Carcinogens; D018336:Receptors, Aryl Hydrocarbon