Determining the role of ERbeta in the activation of ERK1/2 by the environmental estrogens, cadmium chloride and sodium arsenite, in human lung adenocarcinoma cells

Estrogen is involved in the proliferation of adenocarcinoma lung cells. However, the proliferative role of two endocrine disrupters, cadmium chloride and sodium arsenite, in lung adenocarcinoma is less clear. Previous studies have shown that these two heavy metals can induce cellular proliferation and activate phosphorylation of ERK1/2 in a human lug adenocarcinoma cell line, NCI-H1793. Induced phosphorylation of ERK1/2 by these compounds is decreased in the presence of an estrogen receptor antagonist, ICI-182,780, suggesting that cadmium and arsenite stimulate these responses, in part, via a non-genomic estrogen signaling pathway. There are three known estrogen receptors, but it is unclear which might be utilized by cadmium or arsenite to activate ERK1/2. The purpose of this study was to determine if estrogen receptor β (ERβ), the predominant estrogen receptor in lung tissue, induces activation of ERK1/2 upon stimulation with cadmium and arsenite. NCI-H1793 adenocarcinoma lung cells were treated with the ERβ antagonist, PHTPP, before cells were treated for ten minutes with nanomolar concentrations of 17β-estradiol, cadmium chloride, or sodium arsenite. Western blot analysis was used to determine phosphorylation levels of ERK1/2. These results support that cadmium chloride and sodium arsenite induce phosphorylation of ERK1/2 as expected. However, overstimulation of ERK1/2 by PHTPP alone made it difficult to determine if ERβ is involved in cadmium and arsenite stimulated ERK1/2 activation