Cross talk between epidermal growth factor (EGF) receptor and extra nuclear steroid receptors in cell lines

Steroid receptors act as ligand-dependent transcriptional factors. It has been observed that in addition to responding to cognate hormones with transcription activation, once hormone bound they are also capable of rapid responses following association with signaling effectors in the extra nuclear compartment. This novel aspect of steroid hormone action could influence our view of the cross talk between growth factor and steroid receptors. Increasing evidence shows that in hormone-responsive cells, a cross talk occurs between growth factors (EGF, IGF-1) and steroid hormone receptors that reciprocally regulate their action. To date, this has mostly been explained by modulation of steroid receptor transcriptional activity through growth factor receptor signaling activation. However, it is now known that growth factors might also act on extra nuclear steroid receptors, activating them via a hormone-independent mechanism. On the other hand, extra nuclear steroid receptors can regulate growth factor receptor activity either directly interfering with their transduction pathways, or inducing autocrine growth factor secretion. Here we discuss findings indicating that EGF, like steroid hormones, induces association of steroid receptors with Src thereby activating pathways that can trigger cell proliferation and migration. Since mammary and prostate cancers respond to both steroid hormones and growth factors, this association might be a putative target for human cancer therapy. Findings from our laboratory supporting this view are discussed.