Journal
TOXICOLOGICAL SCIENCES
Volume 152, Issue 1, Pages 62-71Publisher
OXFORD UNIV PRESS
DOI: 10.1093/toxsci/kfw064
Keywords
arsenic; arsenite; cadmium; endocrine disruptor; estrogen receptor; GPER; lung cancer; ERK1/2; MAPK
Categories
Funding
- Kentucky National Science Foundation Experimental Program to Stimulate Competitive Research (EPSCoR) grant
- Kentucky Science and Technology Corporation [CFDA 47.076]
- Department of Biology at Bellarmine University
- Kentucky Lung Cancer Research program
- University of Louisville School of Medicine
Ask authors/readers for more resources
Epidemiological evidence indicates that cadmium and arsenic exposure increase lung cancer risk. Cadmium and arsenic are environmental contaminants that act as endocrine disruptors (EDs) by activating estrogen receptors (ERs) in breast and other cancer cell lines but their activity as EDs in lung cancer is untested. Here, we examined the effect of cadmium chloride (CdCl2) and sodium arsenite (NaAsO2) on the proliferation of human lung adenocarcinoma cell lines. Results demonstrated that both CdCl2 and NaAsO2 stimulated cell proliferation at environmentally relevant nM concentrations in a similar manner to 17 beta-estradiol (E-2) in H1793, H2073, and H1944 cells but not in H1792 or H1299 cells. Further studies in H1793 cells showed that 100 nM CdCl2 and NaAsO2 rapidly stimulated mitogen-activated protein kinase (MAPK, extracellular-signal-regulated kinases) phosphorylation with a peak detected at 15 min. Inhibitor studies suggest that rapid MAPK phosphorylation by NaAsO2, CdCl2, and E-2 involves ER, Src, epidermal growth factor receptor, and G-protein coupled ER (GPER) in a pertussis toxin-sensitive pathway. CdCl2 and E-2 activation of MAPK may also involve ER beta. This study supports the involvement of membrane ER and GPER signaling in mediating cellular responses to environmentally relevant nM concentrations of CdCl2 and NaAsO2 in lung adenocarcinoma cells.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available