Recent discoveries suggest that several protein kinases are rapidly activated in response to ligand binding to cytoplasmic steroid hormone receptors (SRs), including progesterone receptors (PRs). Thus, PRs act as ligand-activated transcription factor "sensors" for growth factor-initiated signaling pathways in hormonally regulated tissues, such as the breast. Induction of rapid signaling upon progestin binding to PR-B provides a means to ensure that receptors and co-regulators are appropriately phosphorylated as part of optimal transcription complexes. Alternatively, PR-B activated kinase cascades provide additional avenues for progestin-regulated gene expression independent of PR nuclear action. Herein, an overview of progesterone/PR and signaling cross-talk in breast cancer models is provided. Kinases are emerging as key mediators of PR 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, and is suspected to contribute to cancer biology.
|Original language||English (US)|
|Number of pages||10|
|Journal||Journal of Steroid Biochemistry and Molecular Biology|
|State||Published - Feb 2008|
Copyright 2008 Elsevier B.V., All rights reserved.
- Breast cancer
- Cyclin D1
- Epidermal growth factor
- Mitogen activated protein kinase
- Progesterone receptor
- c-Src kinase