ArticleCancer research2009
Stimulating the GPR30 estrogen receptor with a novel tamoxifen analogue activates SF-1 and promotes endometrial cell proliferation.
Article in Cancer research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 2 of them syntheses that pooled it.
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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.
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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
79 citing papers in PubMed, 2 syntheses or guidelines pooled it, 151 citations in OpenAlex.
- Pharmaceuticals targeting signaling pathways of endometriosis as potential new medical treatment: A review.Medicinal research reviews · 2021Pooled it
- Integrated Bioinformatics, Environmental Epidemiologic and Genomic Approaches to Identify Environmental and Molecular Links between Endometriosis and Breast Cancer.International journal of molecular sciences · 2015Pooled it
- Association of GPR30 Genetic Variants with Recurrent Implantation Failure: A Case-Control Study Comparing Fertile Women, ART Success and RIF Patients.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Molecular Insights Into Endometriosis for Early Detection and Therapeutic Targets.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- Emerging signal transduction pathways and the role of bacterial extracellular vesicles linked to the pathogenesis of endometriosis.Communications medicine · 2026Review
- Expression and purification of Steroidogenic Factor-1 (NR5A1) nuclear receptor ligand binding domain complexed with the signaling phosphoinositide lipid PI(3,4,5)PMethods in enzymology · 2026Article
- Potential endogenous lipid ligands for the nuclear receptor transcription factor Steroidogenic Factor-1.Advances in biological regulation · 2026Review
- Precision Therapeutic and Preventive Molecular Strategies for Endometriosis-Associated Infertility.International journal of molecular sciences · 2025Review
- Cardamomin Inhibits the Proliferation and Tumorigenesis of Bladder Cancer by ESR1 in PI3K/AKT Pathway.Biochemical genetics · 2025Article
- Neuroprotection against beta-amyloid toxicity by the novel estrogen receptor modulator STX requires convergent signaling pathways.Frontiers in molecular neuroscience · 2025Article
- Selective Estrogen Receptor Modulators' (SERMs) Influence onInternational journal of molecular sciences · 2024Article
- GPER/PKA-Dependent Enhancement of Hormone-Sensitive Lipase Phosphorylation in 3T3-L1 Adipocytes by Piceatannol.Nutrients · 2023Article
- SF-1 Induces Nuclear PIP2.Biomolecules · 2023Article
- Comparative G-Protein-Coupled Estrogen Receptor (GPER) Systems in Diabetic and Cancer Conditions: A Review.Molecules (Basel, Switzerland) · 2022Review
- Assessment of G Protein-Coupled Oestrogen Receptor Expression in Normal and Neoplastic Human Tissues Using a Novel Rabbit Monoclonal Antibody.International journal of molecular sciences · 2022Article
- Unveiling the Pathogenesis of Adenomyosis through Animal Models.Journal of clinical medicine · 2022Review
- Review
- Estrogen Receptor Function: Impact on the Human Endometrium.Frontiers in endocrinology · 2022Review
- Review
- Autophagy in the physiological endometrium and cancer.Autophagy · 2021Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Estrogens and selective estrogen receptor (ER) modulators such as tamoxifen are known to increase uterine cell proliferation. Mounting evidence suggests that estrogen signaling is mediated not only by ERalpha and ERbeta nuclear receptors, but also by GPR30 (GPER), a seven transmembrane (7TM) receptor. Here, we report that primary human endometriotic H-38 cells express high levels of GPR30 with no detectable ERalpha or ERbeta. Using a novel tamoxifen analogue, STX, which activates GPR30 but not ERs, significant stimulation of the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways was observed in H-38 cells and in Ishikawa endometrial cancer cells expressing GPR30; a similar effect was observed in JEG3 choriocarcinoma cells. STX treatment also increased cellular pools of phosphatidylinositol (3,4,5) triphosphate, a proposed ligand for the nuclear hormone receptor SF-1 (NR5A1). Consistent with these findings, STX, tamoxifen, and the phytoestrogen genistein were able to increase SF-1 transcription, promote Ishikawa cell proliferation, and induce the SF-1 target gene aromatase in a GPR30-dependent manner. Our findings suggest a novel signaling paradigm that is initiated by estrogen activation of the 7TM receptor GPR30, with signal transduction cascades (PI3K and MAPK) converging on nuclear hormone receptors (SF-1/LRH-1) to modulate their transcriptional output. We propose that this novel GPR30/SF-1 pathway increases local concentrations of estrogen, and together with classic ER signaling, mediate the proliferative effects of synthetic estrogens such as tamoxifen, in promoting endometriosis and endometrial cancers.
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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.