Characterization of MCF mammary epithelial cells overexpressing the Arylhydrocarbon receptor (AhR).

Background: Recent reports indicate the existence of breast cancer cells expressing very high levels of the Arylhydrocarbon receptor (AhR), a ubiquitous intracellular receptor best known for mediating toxic action of dioxin and related pollutants. Positive correlation between the degree of AhR overexpression and states of increasing transformation of mammary epithelial cells appears to occur in the absence of any exogenous AhR ligands. These observations have raised many questions such as why and how AhR is overexpressed in breast cancer and its physiological roles in the progression to advanced carcinogenic transformation.

Arylhydrocarbon receptor activation in NCI-H441 cells and C57BL/6 mice: possible mechanisms for lung dysfunction.

The arylhydrocarbon receptor (AhR) is known for its ability to bind aromatic-containing compounds, which starts a molecular cascade involving the induction of cytochrome P450s and inflammatory cytokines. Our hypothesis is that many inhaled environmental toxicant components activate these inflammatory pathways via an initial binding to the AhR. To test this possibility, we treated Clara cell-derived NCI-H441 cells with the AhR agonist, 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD), and demonstrated that AhR activation increased the expression of both cytochrome P450 s and inflammatory markers.

Promotion of breast cancer by beta-hexachlorocyclohexane in MCF10AT1 cells and MMTV-neu mice.

Background: Exposure to beta-Hexachlorocyclohexane (beta-HCH), a contaminant of the hexachlorohexane pesticide lindane, has been implicated as a risk factor in the development of breast cancers in epidemiological studies. Previous studies in our laboratory have demonstrated the ability of beta-HCH to elicit its actions via a ligand-independent activation of the estrogen receptor through increased c-Neu (= erbB2 or HER-2) expression and kinase activation in both the BG-1 and MCF-7 cell lines. In addition, long term exposure (33 passages) to beta-HCH was shown to promote the selection of MCF-7 cells which exhibit a more metastatic phenotype.

Serum free BG-1 cell proliferation assay: a sensitive method for determining organochlorine pesticide estrogen receptor activation at the nanomolar range.

Most xenobiotic estrogeniety assay methods rely on direct agonist action on the estrogen receptor (ER) to approximate activation potential. Such methods do have drawbacks since some ER activating pesticides are weak or non-agonistic in ligand-binding assays. This study discusses a method that detects pesticide estrogenic actions regardless of ER ligand binding ability.