Activation of membrane estrogen receptor: MAPK signaling by cadmium chloride and sodium arsenite in human lung adenocarcinoma cells

Estrogens have been implicated in non‐small cell lung cancer (NSCLC) risk but the contribution and possible mechanisms of the endocrine disruptors, cadmium chloride (CdCl 2 ) and sodium arsenate (NaAsO 2 ), have not been delineated. In this study, cell proliferation of NCI‐H1793 human lung adenocarcinoma cells increased following treatment with nanomolar concentrations of CdCl 2 and NaAsO 2 , and like 17β‐estadiol (E 2 ), 10 min treatment stimulated phosphorylation of ERK1/2. In the presence of ICI 182,780, an estrogen receptor (ER) antagonist, CdCl 2 and NaAsO 2 ‐stimulated phosphorylation of ERK1/2 was decreased suggesting that activation is mediated through ERs. To identify the role of the ERs in CdCl 2 and NaAsO 2 ‐induced ERK1/2 phosphorylation, cells were treated with specific inhibitors for ERα, ERβ, and the G‐protein linked estrogen receptor (GPER), and ERK1/2 phosphorylation was measured by immunoblot analysis. The results suggest that CdCl 2 and E 2 activation of MAPK phosphorylation likely involves ERβ whereas ERα may play a minor role in NaAsO 2 ‐stimulated MAPK activation. This study supports the involvement of membrane ER and GPER signaling in mediating cellular responses to environmentally relevant nanomolar concentrations of CdCl 2 and NaAsO 2 in lung adenocarcinoma cells.