The role of orphan nuclear receptor DAX-1 (NR0B1) in human breast cancer cells: expression, proliferation and metastasis

<p>The orphan nuclear hormone receptor DAX-1 (Dosage Sensitive Sex Reversal, Adrenal Hypoplasia Congenita on the X Chromosome, gene 1) plays an important role in the development of adrenal and gonadal tissues and functions as a global negative-regulator of steroidogenesis. In addition, it is known to be involved in several diseases including some cancers. Herein, we describe our examination of the role of DAX-1 in breast cancer, specifically its influence on proliferation and metastasis and its expression during progressive stages of disease. In an effort to understand how DAX-1 influences breast cancer cell proliferation and metastasis, we used MCF7 breast cancer cells and MCF10A normal breast cells and manipulated their DAX-1 expression to increase DAX-1 expression by adenovirus infection in MCF7 cells, or knockdown expression of DAX-1 through the use of RNAi in MCF10A cells. We found a trend toward increased cell proliferation when DAX-1 expression was knocked down, and decreased proliferation when DAX-1 is overexpressed. In addition, we looked at the influence of DAX-1 on breast cancer cell proliferation when the estrogen receptor a (ERa) activity is inhibited by the antagonist, Fulvestrant. To gain a better understanding of the transcriptional role of DAX-1 in breast cancer, we utilized PCR arrays to analyze changes in gene expression in the presence of DAX-1. We identified several genes with roles in breast cancer, estrogen receptor signaling and metastasis whose expression was significantly influenced by overexpression of DAX-1 in MCF7 cells. To investigate expression of DAX-1 through progressive stages of disease we utilized IHC and bioinformatics techniques. We found DAX-1 to be expressed more frequently and at higher levels at earlier stages of breast cancers and at very low levels regardless of stage in hormone receptor-positive (ER and PR) patients. Through these studies, we hypothesize that DAX-1 has the potential to be utilized clinically as biomarker for predicting disease progression and for tailoring more personalized treatment plans. There may even be a role for DAX-1 as a possible therapeutic for later stage or hormone receptor-positive patients.</p>

Name thesis:degree_name

Master of Science in Biology

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Biology

Year dc:date.available

2017

Author dc:creator

• Dishington, Erin

Contributors dc:contributor

• Christina Tzagarakis-Foster
• James Sikes
• Jennifer Dever

• DAX-1
• NR0B1
• breast cancer
• orphan nuclear receptor
• NHR
• ONR
• Biology
• Genetics

Repository record dc:identifier

https://repository.usfca.edu/thes/269

OAI identifier oai:identifier

oai:repository.usfca.edu:thes-1348