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Progesterone Receptor Action:

Translating Studies in Breast Cancer Models to Clinical Insights

  • Chapter
Innovative Endocrinology of Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 630))

Abstract

Progesterone receptors (PR) are useful prognostic indicators of breast cancers likely to respond to anti-estrogen receptor (ER) therapies. However, the role of progesterone, therapeutic progestins, or unliganded or liganded PR in breast cancer development or progression remains controversial. PR are ligand-activated transcription factors that act in concert with intracellular signaling pathways as “sensors” of multiple growth factor inputs to hormonally regulated tissues, such as the breast. The recently defined induction of rapid signaling events upon progestin-binding to PR-B provides a means to ensure that receptors and coregulators are appropriately phosphorylated as part of optimal transcription complexes. PR-activated kinase cascades may provide additional avenues for progestin-regulated gene expression independent of PR nuclear action. Herein, we present an overview of progesterone/PR and signaling cross-talk in breast cancer models and discuss the potential significance of progestin/PR action in breast cancer biology using examples from both in vitro and in vivo models, as well as limited clinical data. Kinases are emerging as key mediators of PR action. Cross-talk between PR and membrane-initiated signaling events suggests a mechanism for coordinated regulation of gene subsets by mitogenic stimuli in hormonally responsive normal tissues. Dysregulation of this cross-talk mechanism may contribute to breast cancer biology; further studies are needed to address the potential for targeting PR in addition to ER and selected protein kinases as part of more effective breast cancer therapies.

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Authors and Affiliations

  1. Departments of Medicine (Division of Hematology, Oncology and Transplant) and Pharmacology, University of Minnesota Cancer Center, 420 Delaware Street SE, MMC 806, Minneapolis, Minnesota, 55455, USA

    Carol A. Lange

  2. Departments of Medicine, Pathology, and Obstetrics and Gynecology, University of Colorado Health Sciences Center, Aurora, Colorado, USA

    Carol A. Sartorius, Hany Abdel-Hafiz, Monique A. Spillman, Kathryn B. Horwitz & Britta M. Jacobsen

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  1. Carol A. Lange
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  2. Carol A. Sartorius
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  3. Hany Abdel-Hafiz
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  4. Monique A. Spillman
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  5. Kathryn B. Horwitz
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  6. Britta M. Jacobsen
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Correspondence to Carol A. Lange .

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Editors and Affiliations

  1. Laboratory of Oncoendocrinology, Professor N.N. Petrov Research Institute of Oncology, St. Petersburg, Russia

    Lev M. Berstein MD, PhD, DMS

  2. Division of Endocrinology and Metabolism, University of Virginia Health Sciences Center, Charlottesville, Virginia, USA

    Richard J. Santen MD

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Lange, C.A., Sartorius, C.A., Abdel-Hafiz, H., Spillman, M.A., Horwitz, K.B., Jacobsen, B.M. (2008). Progesterone Receptor Action:. In: Berstein, L.M., Santen, R.J. (eds) Innovative Endocrinology of Cancer. Advances in Experimental Medicine and Biology, vol 630. Springer, New York, NY. https://doi.org/10.1007/978-0-387-78818-0_7

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