Integration of Rapid Signaling Events with Steroid Hormone Receptor Action in Breast and Prostate Cancer

Abstract

Steroid hormone receptors (SRs) are ligand-activated transcription factors and sensors for growth factor–initiated signaling pathways in hormonally regulated tissues, such as the breast or prostate. Recent discoveries suggest that several protein kinases are rapidly activated in response to steroid hormone binding to cytoplasmic SRs. Induction of rapid signaling upon SR ligand binding ensures that receptors and coregulators are appropriately phosphorylated as part of optimal transcription complexes. Alternatively, SR-activated kinase cascades provide additional avenues for SR-regulated gene expression independent of SR nuclear action. We provide an overview of SR and signaling cross talk in breast and prostate cancers, using the human progesterone receptor (PR) and androgen receptor (AR) as models. Kinases are emerging as key mediators of SR action. Cross talk between SR and membrane-initiated signaling events suggests a mechanism for coordinate regulation of gene subsets by mitogenic stimuli in hormonally responsive normal tissues; such cross talk is suspected to contribute to cancer biology.