The ERE-luc reporter mouse.

Abstract

Estrogens, by signaling through two nuclear receptors (ERs), ERα and ERβ), can control specific gene networks and modulate target cell activities. In the last decade, cell-based approaches have provided major insights into the transcriptional regulation of ERs at the promoter of target genes where the interplay between ERs and coactivators and corepressors provides the receptors with tissue specificity of action. This is particularly highlighted by the analysis of transcription efficiency of synthetic ligands for ERs such as selective estrogen receptor modulators (SERMs) that may act as agonist in certain organs and antagonists in others. Furthermore, these molecular studies revealed a multiplicity of mechanisms controlling ER transcriptional activation (Maggi et al. 2004). Indeed, the cognate ligand, estrogen, appears not to be an absolute requirement for the activation of ERs (Bunone et al. 1996; Kato et al. 1995; Ma et al. 1994; Power et al. 1991). Several authors reported that growth factors through phosphorylation might stimulate unliganded ER to induce the transcription of selected target genes (Bunone et al. 1996; Kato et al. 1995; Patrone et al. 1996).