Chronic and acute arsenic exposure enhance EGFR expression via distinct molecular mechanisms. (September 2020)

• Record Type: Journal Article
• Authors: Kim, Christine; States, J. Christopher; Ceresa, Brian P.
• Is Part Of: Toxicology in vitro. Volume 67(2020)
• Publication Date: 2020-09
• Subjects: Arsenic -- TGFα -- EGFR -- BEAS-2B; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2020.104925
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: The impacts of acute arsenic exposure (i.e. vomiting, diarrhea, and renal failure) are distinct from those brought about by sustained, low level exposure from environmental sources or drinking of contaminated well water. Chronic arsenic exposure is a risk factor for the development of pulmonary diseases, including lung cancer. How arsenic exposure leads to pulmonary disease is not fully understood. Both acute versus chronic arsenic exposure increase EGFR expression, but do so via distinct molecular mechanisms. BEAS-2B cells were exposed to either acute sodium arsenite (5 μM for 24 h) or chronic sodium arsenite (100 nM for 24 weeks). Cells treated with acute arsenic exhibited a decrease in viability, changes in morphology, and increased mRNA level of BTC. In contrast, during 24 weeks of arsenic exposure, the cells had increased EGFR expression and activity, and increased mRNA and protein levels of TGFα. Further, chronic arsenic treatment caused an increase in cell migration in the absence of exogenous ligand. Elevated TGFα and EGFR expression are features of many non-small cell lung cancers. We propose that lung epithelial cells chronically exposed to low level arsenic increases EGFR signaling via TGFα production to enhance ligand-independent cell migration. Highlights: Acute and chronic arsenic in lung epithelial cells increase EGFR via distinct mechanisms. Acute arsenic exposure changes cell morphology and decreases cell viability. Chronic arsenic increases TGFα mRNA and protein levels and elevates EGFR activity. TGFα and EGFR expression are frequently elevated in non-small cell lung cancers.