ArticleMolecular endocrinology (Baltimore, Md.)2008
Progesterone receptor rapid signaling mediates serine 345 phosphorylation and tethering to specificity protein 1 transcription factors.
Article in Molecular endocrinology (Baltimore, Md.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 1 of them a synthesis that pooled it.
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Who cites it
95 citing papers in PubMed, 1 synthesis or guideline pooled it, 154 citations in OpenAlex.
- Progesterone Receptor Gene Polymorphisms and Breast Cancer Risk.Endocrinology · 2023Pooled it
- Altered Progesterone Receptor Isoform Expression in Endometrial Cells: A Preliminary Immunohistochemical Study in Endometriosis.Journal of clinical medicine · 2026Article
- Progesterone receptors drive advanced breast cancer phenotypes including circulating tumor- and stem-like cell expansion in the context of ESR1 mutation.NPJ breast cancer · 2026Article
- Ligand-Dependent and -Independent Functions of Activation Function 1 of Progesterone Receptor in Genome-Wide Gene Regulation and in Cell Proliferation and Apoptosis of Breast Cancer Cells.International journal of molecular sciences · 2026Article
- IGFBP-6 regulates SH2D4A expression to promote breast cancer cell cycle progression in response to progesterone.Frontiers in endocrinology · 2026Article
- Progesterone receptors drive advanced breast cancer phenotypes including circulating tumor- and stem-like cell expansion in the context ofbioRxiv : the preprint server for biology · 2025Article
- Activation of Genes by Nuclear Receptor/Specificity Protein (Sp) Interactions in Cancer.Cancers · 2025Review
- Hormone Signaling in Breast Development and Cancer.Advances in experimental medicine and biology · 2025Review
- Bio-Pathological Functions of Posttranslational Modifications of Histological Biomarkers in Breast Cancer.Molecules (Basel, Switzerland) · 2024Review
- Progesterone-mediated remodeling of the maternal-fetal interface by a PGRMC1-dependent mechanism.Journal of reproductive immunology · 2024Article
- Insulin-like growth factor binding protein-6 modulates proliferative antagonism in response to progesterone in breast cancer.Frontiers in endocrinology · 2024Article
- Progesterone signaling in the regulation of luteal steroidogenesis.Molecular human reproduction · 2023Review
- DGMP: Identifying Cancer Driver Genes by Jointing DGCN and MLP from Multi-omics Genomic Data.Genomics, proteomics & bioinformatics · 2022Article
- Membrane-Initiated Estrogen, Androgen, and Progesterone Receptor Signaling in Health and Disease.Endocrine reviews · 2022Review
- Review
- The Role of Progesterone Receptors in Breast Cancer.Drug design, development and therapy · 2022Review
- Review
- Evaluation of Expression and Phosphorylation of Progesterone Receptor in Endometrial Stromal Cells of Patients with Recurrent Implantation Failure Compared to Healthy Fertile Women.Reproductive sciences (Thousand Oaks, Calif.) · 2021Article
- Insulin receptor substrate-1 (IRS-1) mediates progesterone receptor-driven stemness and endocrine resistance in oestrogen receptor+ breast cancer.British journal of cancer · 2021Article
- Article
35 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Human progesterone receptors (PR) rapidly activate cytosolic signaling pathways, in addition to their classical function as ligand-activated transcription factors. Using ER+/PR-B+ T47D breast cancer cells, we probed the role of progestin-stimulated rapid PR signaling in the transcriptional regulation of target genes involved in breast cancer cell proliferation. Epidermal growth factor receptor (EGFR) was rapidly activated after a 10-min treatment with R5020. Progestin induced EGFR-, c-Src-, and MAPK-dependent phosphorylation of PR-B on the MAPK consensus site, Ser345. Ser345-phosphorylated PR-B receptors strongly associated with specificity protein 1 (Sp1) transcription factors to regulate PR cell cycle (p21) and growth-promoting (EGFR) target genes whose promoters lack canonical progesterone response element sequences. Inhibitors of EGFR, c-Src, or MAPK activities blocked PR tethering to Sp1 and progestin-stimulated S-phase entry. Mutant PR-B receptors defective for c-Src binding (mPro) were not phosphorylated on Ser345 in response to progestin and failed to interact with Sp1. Hormone-induced complexes containing Sp1 and wild-type PR-B, but not S345A or mPro PR-B, were recruited to Sp1 sites within the endogenous p21 promoter. Progestin-induced S-phase entry was attenuated in T47D cells containing wild-type PR-B and treated with EGFR, c-Src, or MAPK kinase inhibitors or in T47D cells stably expressing mPro or mutant DNA-binding domain PR-B. In sum, rapid progestin-activated PR signaling leads to PR Ser345 phosphorylation and tethering to Sp1. These events are critical for progestin-stimulated regulation of Sp1 target genes and breast cancer cell proliferation. Our data demonstrate the therapeutic potential for PR-targeted breast cancer treatment by exploiting multiple nodes along the PR signaling pathway, including PR-B, EGFR, c-Src, MAPK, or Sp1.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.