title: Progesterone action in breast, uterine, and ovarian cancers.
abstract: Progesterone and progesterone receptors (PRs) are essential for the development and cyclical regulation of hormone-responsive tissues including the breast and reproductive tract. Altered functions of PR isoforms contribute to the pathogenesis of tumors that arise in these tissues. In the breast, progesterone acts in concert with estrogen to promote proliferative and pro-survival gene programs. In sharp contrast, progesterone inhibits estrogen-driven growth in the uterus and protects the ovary from neoplastic transformation. Progesterone-dependent actions and associated biology in diverse tissues and tumors are mediated by two PR isoforms, PR-A and PR-B. These isoforms are subject to altered transcriptional activity or expression levels, differential crosstalk with growth factor signaling pathways, and distinct post-translational modifications and cofactor-binding partners. Herein, we summarize and discuss the recent literature focused on progesterone and PR isoform-specific actions in breast, uterine, and ovarian cancers. Understanding the complexity of context-dependent PR actions in these tissues is critical to developing new models that will allow us to advance our knowledge base with the goal of revealing novel and efficacious therapeutic regimens for these hormone-responsive diseases.
authors.affiliation: HematologyOncology, and Transplantation DivisionDepartments of MedicinePharmacologyMasonic Cancer Center, University of Minnesota, Delivery Code 2812, Cancer Cardiology Research Building, 2231 6th Street SE, Minneapolis, Minnesota 55455, USADivision of Physiology and GrowthDepartment of Animal Science, University of Minnesota, Minneapolis, Minnesota 55108, USA.
authors.forename: Caroline H
authors.initials: CH
authors.lastname: Diep
authors.affiliation: HematologyOncology, and Transplantation DivisionDepartments of MedicinePharmacologyMasonic Cancer Center, University of Minnesota, Delivery Code 2812, Cancer Cardiology Research Building, 2231 6th Street SE, Minneapolis, Minnesota 55455, USADivision of Physiology and GrowthDepartment of Animal Science, University of Minnesota, Minneapolis, Minnesota 55108, USA.
authors.forename: Andrea R
authors.initials: AR
authors.lastname: Daniel
authors.affiliation: HematologyOncology, and Transplantation DivisionDepartments of MedicinePharmacologyMasonic Cancer Center, University of Minnesota, Delivery Code 2812, Cancer Cardiology Research Building, 2231 6th Street SE, Minneapolis, Minnesota 55455, USADivision of Physiology and GrowthDepartment of Animal Science, University of Minnesota, Minneapolis, Minnesota 55108, USA.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Mauro
authors.affiliation: HematologyOncology, and Transplantation DivisionDepartments of MedicinePharmacologyMasonic Cancer Center, University of Minnesota, Delivery Code 2812, Cancer Cardiology Research Building, 2231 6th Street SE, Minneapolis, Minnesota 55455, USADivision of Physiology and GrowthDepartment of Animal Science, University of Minnesota, Minneapolis, Minnesota 55108, USA.
authors.forename: Todd P
authors.initials: TP
authors.lastname: Knutson
authors.affiliation: HematologyOncology, and Transplantation DivisionDepartments of MedicinePharmacologyMasonic Cancer Center, University of Minnesota, Delivery Code 2812, Cancer Cardiology Research Building, 2231 6th Street SE, Minneapolis, Minnesota 55455, USADivision of Physiology and GrowthDepartment of Animal Science, University of Minnesota, Minneapolis, Minnesota 55108, USA HematologyOncology, and Transplantation DivisionDepartments of MedicinePharmacologyMasonic Cancer Center, University of Minnesota, Delivery Code 2812, Cancer Cardiology Research Building, 2231 6th Street SE, Minneapolis, Minnesota 55455, USADivision of Physiology and GrowthDepartment of Animal Science, University of Minnesota, Minneapolis, Minnesota 55108, USA lange047@umn.edu.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Lange
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008954:Models, Biological; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D011374:Progesterone / Q000627:therapeutic use*; D011980:Receptors, Progesterone / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
chemical_list: D011980:Receptors, Progesterone; D011374:Progesterone
keywords: breast cancer; endometrial cancer; isoforms; ovarian cancer; progesterone; progesterone receptor; progestin; uterine