Role of Estrogen Receptor Beta in Monitoring Hormone-Responsive Breast Cancer Cells by Weighing Gene Fusion Process

One of the most common cancers is Breast Cancer (BC), representing a worldwide public health concern. We previously showed estrogen receptor β (ERβ) oncosuppressor activity as significantly affected estrogen-induced early transcription and mRNA splicing in hormone-responsive MCF-7 human BC cell models. Since gene fusion phenomena are recurrent in cancer cells, we performed a transcriptomic analysis (RNAseq) aiming to assess gene fusion events in MCF-7 human BC cell models that expressed estrogen nuclear receptors α/β under early estradiol (E2) stimulation. The genomic reads sequences were aligned on GRCh38 human genome by using RNA STAR, while the star-fusion was used to detect gene fusion events. Results showed a non-significant variability regarding gene fusion events happening between estradiol-stimulated MCF-7E expressing ERβ (ERβ+/ERα−) and non-stimulated MCF-7noE repressing ERβ expression (ERβ−/ERα+), MCF-7 human BC cell models (p > 0.05). Commonly detected gene fusion events between these two (2) BC cell models result in biomarkers of several cancers and as well BC, and are characterized by intra-chromosomal interactions. Findings revealed five (5) gene fusion events specific to MCF-7noE BC cell models in which ERβ gene expression is repressed (ERβ−/ERα+), and recognized as breast cancer biomarkers. Interestingly, results exhibited ERβ expression as inhibiting gene fusion phenomena specific to BC (BC biomarkers) in replying to estradiol (E2) stimulus in monitoring early hormone-responsive MCF-7 human BC cell models (ERβ+/ERα−; MCF-7E). Overall, even if early estrogen hormone stimulation by inducing nuclear ERβ has non-significant impact on gene fusion variability between MCF-7noE (ERβ−/ERα+) and MCF-7E (ERβ+/ERα−) BC cell line models by contrast to the alternative splicing event, our study highlighted onco-suppressor activity of ERβ in hormone-responsive BC cell line model by potentially silencing several gene fusion expression recognized as BC biomarkers. However, further investigation is necessary to comprehend how ERβ monitors gene fusion in BC.