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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
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Published on: November 15, 2013

Role of the aryl hydrocarbon receptor in carcinogenesis and potential as a drug target

Stephen Safe1, Syng-Ook Lee, Un-Ho Jin

  • 1Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, Texas 77843-4466, USA. ssafe@cvm.tamu.edu

Toxicological Sciences : an Official Journal of the Society of Toxicology
|June 18, 2013
PubMed

Insights

The aryl hydrocarbon receptor (AHR) plays a dual role in cancer, promoting some tumors while inhibiting others. Understanding its specific functions could lead to new targeted anticancer therapies.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • The aryl hydrocarbon receptor (AHR) is widely expressed in various tissues and is increasingly recognized for its role in cellular homeostasis and disease.
  • AHR is present in numerous tumor types, cancer cell lines, and animal tumor models, indicating its involvement in cancer development.

Purpose of the Study:

  • To investigate the complex role of the aryl hydrocarbon receptor (AHR) in tumorigenesis across different cancer types.
  • To explore the potential of targeting AHR with selective modulators as a novel anticancer strategy.

Main Methods:

  • Utilized RNA interference, overexpression, and inhibition studies to determine AHR function.
  • Conducted in vivo studies using genetically modified mice (constitutively active AHR, AHR-deficient) and carcinogen-induced tumor models.
  • Examined the effects of AHR ligands with agonist or antagonist activities on tumorigenesis.

Main Results:

  • Knockdown of AHR generally decreased cancer cell proliferation, invasion, and migration.
  • Overexpression of active AHR enhanced stomach and liver cancer development in mice, suggesting a pro-oncogenic role.
  • Loss of AHR increased carcinogenesis in models of spontaneous colonic tumors and carcinogen-induced liver tumors, indicating an antitumorigenic role prior to tumor formation.
  • AHR ligands demonstrated tumor-specific effects, either enhancing or inhibiting tumorigenesis.

Conclusions:

  • The aryl hydrocarbon receptor (AHR) exhibits context-dependent, dual roles in cancer, acting as both a promoter and inhibitor of tumor development.
  • Selective AHR modulators (SAMs) with specific agonist or antagonist activities represent a promising new class of targeted anticancer agents for diverse tumor types.
Keywords:
Ah receptoragonist activityantagonist activitydrug target.

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