ArticleMolecular biology of the cell2013
Progesterone receptor isoforms PRA and PRB differentially contribute to breast cancer cell migration through interaction with focal adhesion kinase complexes.
Article in Molecular biology of the cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Signaling Pathway Dissection After Progesterone Receptor Enhancement in an Immortalized Pre-Cancer Fallopian Tube Epithelial Cell Line.International journal of molecular sciences · 2026Article
- Reevaluating the Role of Progesterone in Ovarian Cancer: Is Progesterone Always Protective?Endocrine reviews · 2023Article
- Effects of the Overexpression of Progesterone Receptors on a Precancer p53 and Rb-Defective Human Fallopian Tube Epithelial Cell Line.International journal of molecular sciences · 2023Article
- The metastatic capacity of high-grade serous ovarian cancer cells changes along disease progression: inhibition by mifepristone.Cancer cell international · 2022Article
- Progesterone Receptors Promote Quiescence and Ovarian Cancer Cell Phenotypes via DREAM in p53-Mutant Fallopian Tube Models.The Journal of clinical endocrinology and metabolism · 2021Article
- 90 YEARS OF PROGESTERONE: Molecular mechanisms of progesterone receptor action on the breast cancer genome.Journal of molecular endocrinology · 2020Review
- Progesterone through Progesterone Receptor B Isoform Promotes Rodent Embryonic Oligodendrogenesis.Cells · 2020Article
- A-Kinase Anchoring Protein 13 (AKAP13) Augments Progesterone Signaling in Uterine Fibroid Cells.The Journal of clinical endocrinology and metabolism · 2019Article
- Cadmium induces progesterone receptor gene expression via activation of estrogen receptor in human ovarian cancer cells.Research in pharmaceutical sciences · 2018Article
- Progesterone receptor isoforms, agonists and antagonists differentially reprogram estrogen signaling.Oncotarget · 2018Article
- Endocrine Disrupting Chemicals Mediated through Binding Androgen Receptor Are Associated with Diabetes Mellitus.International journal of environmental research and public health · 2017Review
- Progesterone suppresses the invasion and migration of breast cancer cells irrespective of their progesterone receptor status - a short report.Cellular oncology (Dordrecht, Netherlands) · 2017Article
- Exploring Flexibility of Progesterone Receptor Ligand Binding Domain Using Molecular Dynamics.PloS one · 2016Article
- Ulipristal Acetate Inhibits Progesterone Receptor Isoform A-Mediated Human Breast Cancer Proliferation and BCl2-L1 Expression.PloS one · 2015Article
- Progesterone receptor signaling in the initiation of pregnancy and preservation of a healthy uterus.The International journal of developmental biology · 2014Review
- A new strategy for selective targeting of progesterone receptor with passive antagonists.Molecular endocrinology (Baltimore, Md.) · 2013Article
- The dynamics of nuclear receptors and nuclear receptor coregulators in the pathogenesis of endometriosis.Human reproduction updateReview
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Progesterone receptor (PR) and progestins affect mammary tumorigenesis; however, the relative contributions of PR isoforms A and B (PRA and PRB, respectively) in cancer cell migration remains elusive. By using a bi-inducible MDA-MB-231 breast cancer cell line expressing PRA and/or PRB, we analyzed the effect of conditional PR isoform expression. Surprisingly, unliganded PRB but not PRA strongly enhanced cell migration as compared with PR(-) cells. 17,21-Dimethyl-19-norpregna-4,9-dien-3,20-dione (R5020) progestin limited this effect and was counteracted by the antagonist 11β-(4-dimethyl-amino)-phenyl-17β-hydroxy-17-(1-propynyl)-estra-4,9-dien-3-one (RU486). Of importance, PRA coexpression potentiated PRB-mediated migration, whereas PRA alone was ineffective. PR isoforms differentially regulated expressions of major players of cell migration, such as urokinase plasminogen activator (uPA), its inhibitor plasminogen activator inhibitor type 1, uPA receptor (uPAR), and β1-integrin, which affect focal adhesion kinase (FAK) signaling. Moreover, unliganded PRB but not PRA enhanced FAK Tyr397 phosphorylation and colocalized with activated FAK in cell protrusions. Because PRB, as well as PRA, coimmunoprecipitated with FAK, both isoforms can interact with FAK complexes, depending on their respective nucleocytoplasmic trafficking. In addition, FAK degradation was coupled to R5020-dependent turnovers of PRA and PRB. Such an effect of PRB/PRA expression on FAK signaling might thus affect adhesion/motility, underscoring the implication of PR isoforms in breast cancer invasiveness and metastatic evolution with underlying therapeutic outcomes.
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