ArticleSteroids2016
Progesterone induces progesterone receptor gene (PGR) expression via rapid activation of protein kinase pathways required for cooperative estrogen receptor alpha (ER) and progesterone receptor (PR) genomic action at ER/PR target genes.
Article in Steroids, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 87 citations in OpenAlex.
- The estrogen-progestogen-oxidative stress network in uterine fibroids: mechanistic insights and therapeutic opportunities.Redox report : communications in free radical research · 2026Review
- Defining the Role of Progesterone Signaling in High-Grade Serous Ovarian Cancer Using Fallopian Tube Models.Research square · 2026Article
- Nuclear FGF2, androgen receptor and Wnt pathway activation define a targetable subset of antiprogestin-resistant luminal breast cancer.British journal of cancer · 2026Article
- Influences of dietary guanidinoacetic acid supplementation on performance and proteins involved in milk fat and protein synthesis in dairy cows.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Article
- Integrative Network Pharmacology and Molecular Docking-Based Validation of Berberine as a Therapeutic Agent in Arsenic-Induced Cardiotoxicity.Cardiovascular toxicology · 2026Article
- ERFrontiers in oncology · 2026Review
- Identification of a nuclear transcriptional module associated with ERα and E2F/FOXM1 signaling across PAM50 breast cancer subtypes.Frontiers in oncology · 2026Article
- Multitarget Design of Steroidal Inhibitors Against Hormone-Dependent Breast Cancer: An Integrated In Silico Approach.International journal of molecular sciences · 2025Article
- Topological Distribution of the Sex Hormone Receptor Expressions Highlights the Importance of Stromal ERα and Epithelial PR in Malignant Transformation of the Uterine Cervix.International journal of molecular sciences · 2025Article
- Interdependency of estradiol-mediated ERα activation and subsequent PR and GREB1 induction to control cell cycle progression.Heliyon · 2024Article
- Transcriptomic Analysis of Pubertal and Adult Virgin Mouse Mammary Epithelial and Stromal Cell Populations.Journal of mammary gland biology and neoplasia · 2024Article
- Low progesterone receptor levels in high-grade DCIS correlate with HER2 upregulation and the presence of invasive components.Frontiers in oncology · 2024Article
- Differential Effect of 4Current medicinal chemistry · 2024Article
- ERα/PR crosstalk is altered in the context of the ERα Y537S mutation and contributes to endocrine therapy-resistant tumor proliferation.NPJ breast cancer · 2023Article
- Endometrial Progesterone and Estrogen Receptors in Relation to Hormonal Levels in Women with Unexplained Recurrent Miscarriage.Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia · 2023Article
- SCR-6852, an oral and highly brain-penetrating estrogen receptor degrader (SERD), effectively shrinks tumors both in intracranial and subcutaneous ER + breast cancer models.Breast cancer research : BCR · 2023Article
- Progesterone signaling in the regulation of luteal steroidogenesis.Molecular human reproduction · 2023Review
- Gene Expression Profile of Uterine Leiomyoma from Women Exposed to Different Air Pollution Levels in Metropolitan Cities of Sao Paulo, Brazil.International journal of molecular sciences · 2023Article
- Review
- Progesterone Induces Apoptosis and Steroidogenesis in Porcine Placental Trophoblasts.Animals : an open access journal from MDPI · 2022Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Progesterone Receptors (PRs) are critical effectors of estrogen receptor (ER) signaling required for mammary gland development and reproductive proficiency. In breast and reproductive tract malignancies, PR expression is a clinical prognostic marker of ER action. While estrogens primarily regulate PR expression, other factors likely contribute to a dynamic range of receptor expression across diverse tissues. In this study, we identified estrogen-independent but progestin (R5020)-dependent regulation of ER target genes including PGR in ER+/PR+ cancer cell lines. R5020 (10nM-10μM range) induced dose-dependent PR mRNA and protein expression in the absence of estrogen but required both PR and ERα. Antagonists of either PR (RU486, onapristone) or ERα (ICI 182,780) attenuated R5020 induction of TFF1, CTSD, and PGR. Chromatin immunoprecipitation (ChIP) assays performed on ER+/PR+ cells demonstrated that both ERα and PR were recruited to the same ERE/Sp1 site-containing region of the PGR proximal promoter in response to high dose progestin (10μM). Recruitment of ERα and PR to chromatin and subsequent PR mRNA induction were dependent upon rapid activation of MAPK/ERK and AKT; inhibition of these kinase pathways via U0126 or LY294002 blocked these events. Overall, we have identified a novel mechanism of ERα activation initiated by rapid PR-dependent kinase pathway activation and associated with phosphorylation of ERα Ser118 for estrogen-independent but progestin-dependent ER/PR cross talk. These studies may provide insight into mechanisms of persistent ER-target gene expression during periods of hormone (i.e. estrogen) ablation and suggest caution following prolonged treatment with aromatase or CYP17 inhibitors (i.e. contexts when progesterone levels may be abnormally elevated).
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Registered trials
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.