The endocrine disruptors cadmium chloride and sodium arsenate activate estrogen receptor‐mediated signaling and induce human lung adenocarcinoma cell proliferation

Recent studies support a role for estrogens in the etiology of non‐small cell lung cancer (NSCLC) but the mechanism of the endocrine disruptors found in cigarette smoke, cadmium chloride and sodium arsenate, remains unknown. This study tested the hypothesis that these endocrine disruptors stimulate NSCLC growth using a similar mechanism. Nanomolar concentrations of cadmium chloride and sodium arsenate stimulated proliferation of human lung adenocarcinoma NCI‐H1793 cells in a manner similar to 17B‐estradiol (E2). When cells were first treated with the estrogen receptor (ER) antagonist ICI 182,780, proliferation was reduced. Also, treatment of H1793 cells transiently transfected with an ERE‐driven luciferase reporter gene with E2, cadmium chloride or sodium arsenate stimulated luciferase activity in an ER‐dependent manner. Further, cadmium chloride and sodium arsenate, like E2, stimulated phosphorylation of ERK1/2 within 15 min of treatment and was reduced in the presence of the ER antagonist ICI 182,780. These studies support the involvement of ER signaling at both the genomic and non‐genomic levels in mediating cellular responses to environmentally relevant concentrations of cadmium chloride and sodium arsenate in human lung adenocarcinoma cells. MOH was supported by a faculty development stipend from Bellarmine University and CMK by a grant from the Kentucky Lung Cancer Research Program.