Figure 1.

Oestrogen receptor (ER) uses pioneer factors to associate with DNA. Two critical proteins involved in tethering ER to the DNA include FOXA1 and GATA3. Both FOXA1 and GATA3 are mutated in primary cancers, whereas ER is mutated in metastases. The impact that these mutations have on ER activity is not known. Recently, the crosstalk between different nuclear receptors has become apparent. Progesterone receptor (PR) and androgen receptor (AR) are commonly expressed in ER⁺ breast cancer and both are known to impinge on ER transcriptional activity. A major challenge involves identifying how we can exploit existing PR and AR ligands for therapeutic use and how the mutations in ER, FOXA1 and GATA3 influence this hormonal crosstalk.