Document Type

Thesis

Date of Completion

Spring 4-29-2022

Department

Biology

Academic Major

Molecular and Cellular Biology

Faculty Advisor

David Donley, Ph.D.

Abstract

Regulation of cellular processes is important for proper functioning. Environmental factors, including stress, can interfere with cellular regulation. One of the diseases caused by cellular regulation disturbance is cancer and mutations in EGF-related genes highly correlate with worse outcomes in cancer. The Epidermal Growth Factor (EGF) pathway is involved in the regulation of cell growth and differentiation. Phosphorylation of the receptors activates this pathway, leading to cell growth and regulation. This study examines the impact of oxidative stress on EGF pathway activation. Previous studies using breast cancer lines have indirectly shown a decrease in Epidermal Growth Factor Receptor (EGFR) activation with titanium dioxide-induced oxidative damage. To directly test the role of free radicals on EGF pathway activation, we measured EGF receptor phosphorylation levels in mouse microglia cells. N-tert-Butyl-a-phenylnitrone, a free radical spin trap, decreased EGFR phosphorylation by approximately 50%. In addition, exposure to Hydrogen Peroxide resulted in prolonged activation of EGF receptors. Exogenous iron treatment was seen to produce similar levels of activation as the control. Exogenous copper treatment was seen to promote hyperactivation of the receptor. These data help elucidate the impact of Reactive Oxygen Species (ROS) and other cellular stressors on EGFR signaling and potential ways to target cell regulation in disease states.

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