The aryl hydrocarbon receptor plays a role in mediating adipocyte/breast cancer interactions

Abstract

The Aryl Hydrocarbon receptor (AHR) is a ligand‐activated transcription factor that mediates the effects of environmental toxicants. Obesity is a risk factor for several types of cancer. Prior reports and our data indicate that adipocytes secrete factors that induce breast cancer cell growth. Herein, we determined if adipocyte secreted factors (ASFs) regulate the expression of AHR responsive genes and induce cancer growth through AHR dependent mechanisms. We found that ASFs suppress ~90% and ~80% of basal CYP1A1 and CYP1B1 expression, respectively. In control MCF‐7 cells, ASFs induced a 3 fold increase in growth in 3 days. In AHR‐knockdown cells, ASFs induced a 2 fold increase in growth in 3 days. AHR antagonists also blocked adipocyte‐stimulated cancer growth. Collectively, these data indicate that ASFs inhibit the expression of “classic” AHR gene targets, and induce growth through AHR dependent mechanisms. This work was supported by P20RR016477 to the West Virginia IDeA Network of Biomedical Research Excellence, Cell Differentiation and Development Center at Marshall University, and Pharmacological Research and Manufactures of America Foundation (PhRMA) Research Starter Grant in Pharmacology/Toxicology.