Therapeutic Targeting of Ovarian Cancer Stem Cells Using Estrogen Receptor Beta Agonist

We examined the transcriptional changes altered by ERß agonist LY500307 treatment in ovarian cancer stem cells (OCSCs) by performing global transcriptome analysis. SKOV3-ALDH+ OCSCs were treated with vehicle or LY500307 (5 µM) for 24 h and the RNA was isolated and utilized for RNA-seq analysis. Our results demonstrated that the top pathways altered by LY500307 were related to cell cycle and apoptosis. Functional enrichment using GSEA analysis showed that LY500307-regulated genes showed positive enrichment in the p53 pathway, oxidative phosphorylation, apoptosis and estrogen late response genes, and negative correlation with E2F targets, G2/M checkpoint and mitotic spindle. Overall design: SKOV3-ALDH+ OCSCs were treated with vehicle or LY500307 (5 µM) for 24 h and the total RNA was isolated using RNeasy Mini Kit (Qiagen, Valencia, CA). Illumina TruSeq RNA Sample Preparation was performed following manufacturer's protocol. Samples were run on an Illumina HiSeq 3000 in duplicate. The combined raw reads were aligned to UCSC hg19 and genes were annotated by Tophat. Genes were annotated and quantified by HTSeq-DESeq pipeline.