ArticlePloS one2020
Plasma membrane expression of G protein-coupled estrogen receptor (GPER)/G protein-coupled receptor 30 (GPR30) is associated with worse outcome in metachronous contralateral breast cancer.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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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
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Cytoplasmic G Protein-Coupled Estrogen Receptor 1 as a Prognostic Indicator of Breast Cancer: A Meta-Analysis.Technology in cancer research & treatmentPooled it
- Missense mutations of GPER1 in breast invasive carcinoma: Exploring gene expression, signal transduction and immune cell infiltration with insights from cellular pharmacology.Biomedical reports · 2025Article
- The GPR30 Receptor Is Involved in IL-6-Induced Metastatic Properties of MCF-7 Luminal Breast Cancer Cells.International journal of molecular sciences · 2024Article
- G protein-coupled estrogen receptor (GPER)/GPR30 forms a complex with the βArchives of biochemistry and biophysics · 2024Article
- Oestrogen receptor-independent actions of oestrogen in cancer.Molecular biology reports · 2023Review
- Locomotion Outcome Improvement in Mice with Glioblastoma Multiforme after Treatment with Anastrozole.Brain sciences · 2023Article
- Roles of Estrogen, Estrogen Receptors, and Estrogen-Related Receptors in Skeletal Muscle: Regulation of Mitochondrial Function.International journal of molecular sciences · 2023Review
- Comparative G-Protein-Coupled Estrogen Receptor (GPER) Systems in Diabetic and Cancer Conditions: A Review.Molecules (Basel, Switzerland) · 2022Review
- High GPER expression in triple-negative breast cancer is linked to pro-metastatic pathways and predicts poor patient outcomes.NPJ breast cancer · 2022Article
- 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
- The G-Protein-Coupled Estrogen Receptor Agonist G-1 Inhibits Proliferation and Causes Apoptosis in Leukemia Cell Lines of T Lineage.Frontiers in cell and developmental biology · 2022Article
- Review
- Ligand-Independent G Protein-Coupled Estrogen Receptor/G Protein-Coupled Receptor 30 Activity: Lack of Receptor-Dependent Effects of G-1 and 17Molecular pharmacology · 2021Article
- Exploiting off-target effects of estrogen deprivation to sensitize estrogen receptor negative breast cancer to immune killing.Journal for immunotherapy of cancer · 2021Article
- The impact of G protein-coupled oestrogen receptor 1 on male breast cancer: a retrospective analysis.Contemporary oncology (Poznan, Poland) · 2021Article
- GPER and Testicular Germ Cell Cancer.Frontiers in endocrinology · 2020Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundG protein-coupled estrogen receptor (GPER), or G protein-coupled receptor 30 (GPR30), is reported to mediate non-genomic estrogen signaling. GPR30 associates with breast cancer (BC) outcome and may contribute to tamoxifen resistance. We investigated the expression and prognostic significance of GPR30 in metachronous contralateral breast cancer (CBC) as a model of tamoxifen resistance.
methodsTotal GPR30 expression (GPR30TOT) and plasma membrane-localized GPR30 expression (GPR30PM) were analyzed by immunohistochemistry in primary (BC1; nBC1 = 559) and contralateral BC (BC2; nBC2 = 595), and in lymph node metastases (LGL; nLGL1 = 213; nLGL2 = 196). Death from BC (BCD), including BC death or death after documented distant metastasis, was used as primary end-point.
resultsGPR30PM in BC2 and LGL2 were associated with increased risk of BCD (HRBC2 = 1.7, p = 0.03; HRLGL2 = 2.0; p = 0.02). In BC1 and BC2, GPR30PM associated with estrogen receptor (ER)-negativity (pBC1<0.0001; pBC2<0.0001) and progesterone receptor (PR)-negativity (pBC1 = 0.0007; pBC2<0.0001). The highest GPR30TOT and GPR30PM were observed in triple-negative BC. GPR30PM associated with high Ki67 staining in BC1 (p<0.0001) and BC2 (p<0.0001). GPR30TOT in BC2 did not associate with tamoxifen treatment for BC1. However, BC2 that were diagnosed during tamoxifen treatment were more likely to express GPR30PM than BC2 diagnosed after treatment completion (p = 0.01). Furthermore, a trend was observed that patients with GPR30PM in an ER-positive BC2 had greater benefit from tamoxifen treatment.
conclusionPM-localized GPR30 staining is associated with increased risk of BC death when expressed in BC2 and LGL2. Additionally, PM-localized GPR30 correlates with prognostic markers of worse outcome, such as high Ki67 and a triple-negative subtype. Therefore, PM-localized GPR30 may be an interesting new target for therapeutic exploitation. We found no clear evidence that total GPR30 expression is affected by tamoxifen exposure during development of metachronous CBC, or that GPR30 contributes to tamoxifen resistance.
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