title: Integration of progesterone receptor action with rapid signaling events in breast cancer models.
abstract: 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.
authors.affiliation: University of Minnesota Cancer Center, Department of Medicine, Division of Hematology, Oncology, and Transplant, 420 Delaware Street SE, Minneapolis, MN 55455, USA. Lange047@umn.edu
authors.forename: Carol A
authors.initials: CA
authors.lastname: Lange
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000209:etiology / Q000503:physiopathology*; D019938:Cyclin D1 / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D005260:Female; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation; D011980:Receptors, Progesterone / Q000502:physiology*; D011987:Receptors, Steroid / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D011980:Receptors, Progesterone; D011987:Receptors, Steroid; D019938:Cyclin D1; D051357:Cyclin-Dependent Kinase 2; D020928:Mitogen-Activated Protein Kinases