Abstract 4402: FGFR1 signaling modulates estrogen-independent ER transcriptional activity in ER+/FGFR1-amplified breast cancer cells

Background: FGFR1 amplification occurs in about 15% of estrogen receptor-positive (ER+) breast cancers and is associated with resistance to endocrine therapy. In these tumors, nuclear FGFR1 has been shown to interact with ERα. In addition, FGFR1 has been demonstrated to alter gene expression through binding to chromatin. However, the mechanisms underpinning nuclear FGFR1-mediated gene transcription remain unclear. Thus, we sought to elucidate the genomic and non-genomic role of FGFR1 in ER+/FGFR1-amplified breast cancer. Methods: FGFR1 ChIP-Seq and ERα ChIP-Seq were performed on CAMA1 ER+/FGFR1-amplified breast cancer cells. ChIP-qPCR was employed to quantify DNA binding events. For ChIP-Seq, immunoblot, RT-qPCR, Estrogen Response Element (ERE) luciferase reporter and growth assays, CAMA1 cells were plated in estrogen-free media for 24 hours and then stimulated with 100 ng/ml FGF3 or 1 nM β-Estradiol. Results: FGFR1 ChIP-Seq detected 2211 DNA binding sites in CAMA1 cells cultured in estrogen-free conditions. Gene Set Enrichment Analysis (GSEA) revealed that the TNFα signaling via NF-KB, MYC targets, G2M checkpoints, ERE early and ERE late response genes (all FDR