Date of Graduation

Fall 12-13-2019

Document Type

Thesis

Degree Name

Master of Science in Biology

College/School

College of Arts and Sciences

Department/Program

Biology

First Advisor

Dr. Christina Tzagarakis-Foster

Second Advisor

Dr. Mary Jane Niles

Third Advisor

Dr. John Paul

Abstract

Prostate cancer (PCa) is estimated to be the second leading cause of cancer-related deaths among men in the United States in 2019. While most prostate tumors rely on androgens for growth signaling, there are subsets of tumors that become androgen-resistant, therefore resisting conventional androgen-depravation therapy. Consequently, research has focused on targeting different hormone receptors for novel therapeutics. One such receptor is Dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 (DAX-1). DAX-1 is known to interact with other hormone receptors, such as androgen receptor (AR) and estrogen receptors (ERs) to suppress the proliferative effects of their signaling. Little work has been done on the association of ERs and DAX-1 in prostate cancer cells. Therefore, the aim of this project was to explore DAX-1 and ER binding in the context of PCa cell lines. DAX-1, ERα, and Erβ expression was confirmed via PCR and western blot in two different PCa cell lines. Immunofluorescence microscopy was used to determine co-localization of DAX-1 with ERα and DAX-1 with ERβ. This novel finding suggests that the hormone receptors bind in vivo in PCa cell lines. GST pull-down assays along with co-immunoprecipitation assays were then performed to assess bona fide interaction of DAX-1 and ERα. Though results assays were inconclusive, the previous results of hormone receptor co-localization support the idea that DAX-1 does bind ERs in vivo. These results strongly suggest DAX-1 utilizes both ERs as binding partners in PCa cells and potentially mediates their effects in prostate cancer through these interactions.

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