cAMP Signaling Reprograms the Estrogen Receptor α

The estrogen receptor α (ER) belongs to a superfamily of structurally conserved transcription factors, called nuclear receptors (NR). The receptor is activated both by estrogens, including 17β-­‐estradiol (E2), and by a large variety of other extracellular signals (Fig. 1). Several studies have demonstrated that increased levels of cAMP, as commonly occur in breast cancer cells resistant to anti-­‐estrogens such as Tamoxifen, regulate gene expression through the ER, suggesting a redirection of the receptor to an alternate signaling pathway These studies used a combination of microarray analysis and bioinformatics tools as an approach to understand the transcriptional responses of the ER to cAMP and to E2.