Date of Project

5-16-2016

Document Type

Honors Thesis

School Name

College of Arts and Sciences

Department

Biology

Major Advisor

Dr. Mary Huff

Abstract

Nanomolar concentrations of both cadmium and arsenite, two environmental estrogens present in cigarette smoke, have been documented in rapidly phosphorylating ERK1/2, a type of MAPK, in the human non-small cell lung cancer (NSCLC) line NHI-1793 in a manner similar to that of estrogen. Pretreatment of cells with a general, nonspecific estrogen receptor antagonist reduced the levels of phosphorylated MAPK, indicating that this phosphorylation event is achieved through use of an estrogen signaling pathway. The specific estrogen receptor involved in this process, however, is currently unknown. To determine whether GPR30, one of the three types of estrogen receptors, is necessary for the phosphorylation of MAPK, NHI-1793 cells were treated with 17β-estradiol, cadmium chloride, and sodium arsenite both in the presence and absence of G15 – a GPR30-specific antagonist – and MAPK levels were measured using immunoblot analysis. As expected, the data revealed these nanomolar concentrations of endogenous and environmental estrogens were sufficient in phosphorylating ERK1/2 in under ten minutes and pretreatment with G15 reduced phosphorylation in cells treated with 17β estradiol and cadmium chloride, but not in those treated with arsenite. Therefore, cadmium and estradiol likely utilize GPR30 to phosphorylate ERK1/2, while further research is needed to elucidate the mechanism of arsenite-induced ERK1/2 activation. These results are important in understanding the polarity of lung cancer diagnosis and progression between genders, as well as in the development of pharmaceuticals.

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