Assessing the role of arsenite in disrupting the EGFR signaling axis.

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase localized on the cell surface. Overexpression of EGFR has been used as biomarkers for many different types of cancers, including lung cancer. There is a strong association between arsenic and lung cancer development, although the mechanism is unclear. We hypothesize that chronic exposure of “a physiologically relevant” level of arsenite disrupts the EGFR endocytic trafficking. The goal of this project is to identify molecular mechanisms and roles of chronic arsenite-induced EGFR overexpression in lung cancer development. A non-malignant human bronchial epithelial cell line, Beas-2B cells were exposed to 100 nM sodium arsenite for 24 weeks. The chronic arsenite-treated cells had increased EGFR protein expression levels and activity, increased transcription levels of TGFα, and altered the distribution of the EGFR. In conclusion, the impact of chronic arsenite exposure on the EGFR signaling axis can explain arsenite-induced overexpression of the EGFR