[Decoding the mode of action of the estrogen receptor through functional genomics]

Estradiol is a potent growth factor of breast cancer cells and inhibition of its activity has been a basis for the treatment of this disease for a long time. Estradiol exerts its action mainly through a nuclear receptor (ERalpha) that recognizes specific sites in the genome and regulates the transcription of neighboring genes. The identification of the repertoire of estrogen responsive genes is considered an essential step for our comprehension of the biological functions of the hormone and of the molecular mechanisms by which ERalpha control gene expression. The technology combining immunoprecipitation of DNA fragments and hybridization to DNA chips currently allows the rapid identification of transcription factor binding sites on a whole-genome level. The recent utilization of this technology has not only led to the identification of numerous ERalpha target genes in breast cancer cells, but has also revealed that the receptor requires the presence of another transcription factor, known as FOXA1, to activate a specific subset of these genes. These studies have thus shown that factors like FOXA1 can be utilized to compartmentalize the action of the hormone, suggesting new opportunities to target more precisely the action of nuclear receptors for the prevention and treatment of hormone-dependent cancer.