Estrogen receptor regulates hormone-induced growth arrest in a luminal A like breast cancer model

Estrogen receptor positive (ER+) breast cancer has been divided into two subtypes, luminal A and luminal B, which differ in their ER expression and response to hormone therapy. The absence of luminal A cell lines means the extensive amount ofin vitrowork studying the response to hormones in ER+ breast cancers is biased for the luminal B subtype. We have developed a luminal A like cell model by increasing the ER expression in the MCF-7 cell line. Our results show that increased ER expression promotes an anti-proliferative response to estrogen through regulation of genes involved in the G1/S-phase transition of the cell cycle. Furthermore, increased ER expression increases ER-DNA binding in the absence of estrogen and regulates basal gene transcription by promoting DNA looping. These results provide novel evidence that the characteristic increased ER expression of luminal A tumors may promote a novel chromatin configuration that enables growth of these tumors in the absence of estrogen and enables gene repression in the presence of hormones.