Graduation Date

8-2018

Document Type

Master's Thesis

Degree Name

Master of Science

Department or Program

Biological Sciences

Department or Program Chair

Meredith Protas, PhD

First Reader

Maggie Louie, PhD

Second Reader

Mary Sevigny, PhD

Abstract

The global prevalence of breast cancer in women illustrates the importance of identifying factors that contribute to disease onset and progression. Endogenous and environmental agents that interact with estrogen receptor alpha (ERα) have been shown to play a role in breast cancer etiology. Evidence from epidemiological studies and animal models has suggested that cadmium, a heavy metal that can activate ERα, contributes to the development and progression of breast cancer. Additionally, our lab showed that chronic cadmium exposure altered the expression of several ERα-responsive genes and increased the malignancy of MCF7 breast cancer cells. Although these studies support cadmium’s function as a hormone disrupter, the role of ERα in cadmium-induced breast cancer progression remains unclear. Therefore, the goal of this thesis is to better understand how chronic cadmium exposure alters ERα activity and how this contributes to cadmium-induced cancer cell growth and gene expression. To accomplish this, we modulated the expression of ERα in MCF7 cells after chronic cadmium exposure (Cd7 and Cd12) and performed phenotypic and gene expression analyses. Additionally, since breast cancer progression is often associated with resistance to cancer treatment, the effect of chronic cadmium exposure on sensitivity to chemotherapeutic drugs was investigated. Our findings suggest that chronic cadmium exposure contributes to breast cancer progression by increasing the adaptability of cells to ERα loss and highlight a potentially new role for chronic cadmium exposure in determining drug response.

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