Identifying Functional Nuclear Receptor Signaling in Estrogen Receptor-Positive Breast Cancer

We developed a microarray data analytical method capable of identifying ligand-activated nuclear receptors (NRs) in samples of the MCF7 cell line that are cultured among uncharacterized ligands. Principally, we applied this novel technique to reanalyze microarray data from an MCF7 xenograft experiment to reveal NR signaling that is likely the result of small molecule ligands available in the tumor microenvironment. Furthermore, this method was applied to query NR signaling caused by the small molecules present in fetal bovine serum to identify receptors stimulated by this common culture method. These analyses unveiled the potentially important roles of NR5A1 and NR1H4 in the progression of estrogen receptor-positive breast cancer. Preliminary experiments demonstrate that these receptors may play a role in mediating the transcriptional regulatory action of the estrogen receptor itself, potentially opening novel avenues for the development of more efficacious adjuvant therapies.
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Undergraduate Thesis
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