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Targeting the Aryl Hydrocarbon Receptor Signaling Pathway in Breast Cancer Development

Christoph F A Vogel1,2, Gwendal Lazennec3, Sarah Y Kado2

  • 1Department of Environmental Toxicology, University of California, Davis, Davis, CA, United States.

Frontiers in Immunology
|March 25, 2021
PubMed

Insights

The aryl hydrocarbon receptor repressor (AhRR) suppresses breast cancer growth by blocking the aryl hydrocarbon receptor (AhR) pathway. Restoring AhRR function may offer therapeutic benefits for breast cancer patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Environmental Health

Background:

  • The aryl hydrocarbon receptor (AhR) pathway, activated by environmental carcinogens like dioxins, promotes breast cancer.
  • The aryl hydrocarbon receptor repressor (AhRR) inhibits the AhR pathway, but its role in breast cancer is unclear.
  • AhRR is a potential tumor suppressor, frequently silenced in breast cancers, with its loss correlating to poorer patient survival.

Purpose of the Study:

  • To investigate the impact of AhRR on AhR-driven breast cancer development.
  • To determine if AhRR can counteract AhR-mediated tumor promotion.
  • To explore the therapeutic potential of AhRR in breast cancer.

Main Methods:

  • Utilized AhRR transgenic mice and two murine breast cancer models (E0771 and PyMT).
  • Examined the effects of AhRR overexpression and AhR knockout in human breast cancer cells.
  • Assessed tumor growth, inflammation, and apoptosis induction by chemotherapeutics.

Main Results:

  • AhRR overexpression inhibited AhR-driven and inflammation-induced mammary tumor growth in mice.
  • AhRR overexpression or AhR knockout enhanced chemotherapeutic-induced apoptosis in human breast cancer cells.
  • AhRR overexpression inhibited mouse mammary tumor cell growth.

Conclusions:

  • This study provides the first in vivo evidence that AhRR acts as a suppressor of mammary tumor development.
  • Restoring AhRR function and expression may represent a viable therapeutic strategy for breast cancer.
Keywords:
AhRAhRRC/EBPβbreast cancercarcinogenicitycyclooxygenase 2inflammation

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