University Archives

Estrogen receptor alpha (ERɑ) plays a key role in regulating proliferation in hormone-responsive breast cancer cells. Structurally related compound interactions with ERɑ are essential for evaluating estrogenic and anti-estrogenic effects. The purpose of this study is to investigate the proliferation response of breast cancer cells to estradiol (E2) and evaluate ligand receptor interactions through computational analysis. Cells were cultured under estrogen-deprived conditions and treated with E2 with varying concentrations of 1 nM-30 nM. For proliferations, MCF-7 cells were plated at 1,000 cells per well, while T47D cells were plated at 2,000 cells per well. Growth characteristics and metabolic activity were measured using a fluorescence assay after four days of treatment. Fluorescence measurements demonstrated a concentration increase in cellular metabolic activity following E2 treatments, confirming estrogen response under hormone-deselected conditions. T47D cells indicated a slight increase in cell growth with the presence of the minoxidil intermediate whereas MCF-7 cells did not. Molecular docking simulations were also performed to examine ligand binding interactions with ERɑ binding pocket while taking into account the hydrogen bonding and hydrophobic amino acid residues. Computational docking supported these findings by demonstrating binding interactions between ligand structure and ERɑ residues. These results validate the experimental model and the integration of the wet lab and computational work in order to assess ERɑ signaling. This combined study provides an evaluation of the biological relevance of ligand-receptor interactions when dealing with hormone-responsive cancer cells.