(L5285) Estrogen Induces Transcriptomic Changes Associated with Oncogenic Phenotypes in Inflammatory Breast Cancer

Xavier Bittman (University of Puerto Rico - Rio Piedras Campus)| Josue Perez-Santiago (UPR Comprehensive Cancer Center, San Juan, PR)| Esther Peterson (University of Puerto Rico - Rio Piedras Campus)

Inflammatory Breast Cancer (IBC) is rare and the most aggressive subtype of all breast cancers, reporting rapid progression, poor prognosis, and a unique clinical diagnosis. Approximately ~30% of IBC cases are classified as triple negative breast cancer (TNBC), meaning they do not test positive for hormone receptors (estrogen and progesterone) and amplification of the human epidermal growth factor receptor 2 (HER2); therefore limiting the effectiveness of hormonal therapeutics. However, recent studies have reported that estrogen (E2) can induce a rapid E2-response in IBC cells to enhance migration and invasion phenotypes by activation of novel cytoplasmic and membrane localized estrogen receptors (ERα36 isoform and G protein-coupled receptor 30 (GPR30)); both suggested as possible therapeutic targets. However, the role of these receptors in the estrogen genomic signaling pathway remains elusive and there is still no data published related to an E2-induced transcriptional stimulation of genes associated with IBC’s aggressive phenotype. Here, we evaluated gene expression changes related to E2 in IBC cell lines SUM149PT to identify target genes and biological pathways associated with IBC’s aggressive phenotype. We hypothesized that E2 exposure can induce transcriptional stimulation of genes related to migration and invasion phenotypes in IBC cells SUM149PT.

Methods: We performed RNA-seq (Illumina NextSeq PE 2x75bp) in 2 study groups (ETOH-treated and E2-treated) to identify specific changes in the expression of genes associated with migration and invasion in IBC SUM149PT. Functional and enrichment analysis of differentially expressed genes were performed using Metascape. qPCR was performed to validate a subset of genes related to the enriched terms associated with the migration and invasion phenotypes.

Results:  After E2 exposue (3hrs), we have identified 370 significantly dysregulated genes (p < 0.05), including the ZNF268 gene (adj. p-val significant), which can be potential therapeutic targets. Functional annotation of these genes showed association with mammary gland epithelial cell proliferation, actin cytoskeleton organization, and transmembrane receptor protein tyrosine kinase signaling pathway. Data acquired from these experiments will contribute to the better understanding of IBC’s transcriptomic signature and create new opportunities to develop novel targeted therapies.