TY - JOUR
T1 - Integration of progesterone receptor action with rapid signaling events in breast cancer models
AU - Lange, Carol A.
PY - 2008/2
Y1 - 2008/2
N2 - 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.
AB - 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.
KW - Breast cancer
KW - Cyclin D1
KW - Epidermal growth factor
KW - Mitogen activated protein kinase
KW - Progesterone receptor
KW - c-Src kinase
UR - http://www.scopus.com/inward/record.url?scp=38749140218&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38749140218&partnerID=8YFLogxK
U2 - 10.1016/j.jsbmb.2007.09.019
DO - 10.1016/j.jsbmb.2007.09.019
M3 - Review article
C2 - 17964138
AN - SCOPUS:38749140218
SN - 0960-0760
VL - 108
SP - 203
EP - 212
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
IS - 3-5
ER -