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Bi-directional Regulation of Human Progesterone Receptors and the Mitogen Activated Protein Kinase Pathway in Breast Cancer Cell Models

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Hormonal Carcinogenesis IV

Summary

Breast cancers (BCs) often have increased mitogen-activated protein kinase (MAPK) activity. This pathway influences BC cell growth in part by targeting steroid hormone receptors. Activation of p42 and p44 MAPKs increases progesterone receptor (PR) transcriptional activity in the presence of progestins, and triggers their rapid down-regulation by the ubiquitin-proteasome pathway. In turn, progestins increase the expression of type 1 growth factor receptor tyrosine kinases that feed into MAPK activation. Recently, progestins have been shown to activate the p42/p44 MAPK module in a PR-dependent manner, but independently of their function as transcription factors. Mechanisms of bi-directional cross-talk between these two pathways are becoming well-documented. Herein, we provide an overview of the primary ways in which steroid hormone receptor and growth factor cross-talk occurs, using examples from our work with human PR as a model receptor; we demonstrate MAPK regulation of PR subcellular localization, transcriptional synergy, and regulation of cyclin D1 expression. Cross-talk between growth factor and PR-mediated signaling events is an important means by which growth regulatory genes are coordinately regulated, and may contribute to the growth of hormonally responsive normal breast tissue and to BC.

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Author information

Authors and Affiliations

  1. Department of Medicine, Division of Hematology, Oncology, and Transplant, University of Minnesota Cancer Center, Minneapolis, MN, USA

    Carol A. Lange

Authors
  1. Emily Faivre
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  2. Ming Qiu
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  3. Carol A. Lange
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Editor information

Editors and Affiliations

  1. Division of Etiology and Prevention of Hormonal Cancers, The University of Kansas Medical Center, 3901 Rainbow Boulevard, 2010 Breidenthal, Kansas City, KS, 66160-7417

    Jonathan J. Li (Profesor of Pharmacology, Toxicology and Therapeutics and Director) & Sara A. Li (Associate Research Professor of Pharmacology, Toxicology and Therapeutics) (Profesor of Pharmacology, Toxicology and Therapeutics and Director) &  (Associate Research Professor of Pharmacology, Toxicology and Therapeutics)

  2. Departmento de Patologia, Facultad de Medicina y Odontologia, Camino de Vera s/n, Valencia, 46071, Spain

    Antonio Llombart-Bosch (Director) (Director)

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© 2005 Springer Science+Business Media, Inc.

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Faivre, E., Qiu, M., Lange, C.A. (2005). Bi-directional Regulation of Human Progesterone Receptors and the Mitogen Activated Protein Kinase Pathway in Breast Cancer Cell Models. In: Li, J.J., Li, S.A., Llombart-Bosch, A. (eds) Hormonal Carcinogenesis IV. Springer, Boston, MA. https://doi.org/10.1007/0-387-23761-5_37

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  • DOI: https://doi.org/10.1007/0-387-23761-5_37

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-387-23783-1

  • Online ISBN: 978-0-387-23761-9

  • eBook Packages: MedicineMedicine (R0)

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