RNA-seq of estrogen-induced transcriptome in breast cancer cell lines

Oestrogen receptor alpha (ERa/ESR1) is upregulated in the majority of breast tumours and drives tumour proliferation. Thus, ERa-positive tumours are commonly treated with ERa antagonists or inhibitors of oestrogen synthesis. Although initially successful, most tumours develop resistance towards these treatments and there is an urgent need to determine the pathways that underlie the proliferative and tumorigenic role of this receptor, in order to design novel strategies to battle tumours that are treatment insensitive. ERa is a ligand-activated transcription factor that exerts its main functions through the regulation of target genes. We here present the first single-molecule sequencing of the oestradiol-induced ERa transcriptome in the human breast cancer cell lines MCF7 and T47D. We confirm previously characterised target genes and define novel targets. Furthermore, we uncover major oestrogen-mediated regulations of long non-coding RNAs (lncRNAs) in both cell lines. We demonstrate that lncRNAs are direct transcriptional targets of ERa, correlate to ERa expression in clinical samples, and show prognostic significance in relation to breast cancer survival. Our findings suggest that ERa mediates substantial activity through its transcriptional regulation of lncRNAs and that this novel function of ERa may be critical for its protein-regulatory functions.