ArticleBreast cancer research : BCR2013
GPR30 as an initiator of tamoxifen resistance in hormone-dependent breast cancer.
Article in Breast cancer research : BCR, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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76 citing papers in PubMed, 131 citations in OpenAlex.
- Endocrine therapy resistance of breast cancer: Important role of G protein-coupled estrogen receptor (GPER) and new therapeutic strategies.Genes & diseases · 2026Review
- GPER in metabolic homeostasis and disease: molecular mechanisms, nutritional regulation, and therapeutic potential.Journal of translational medicine · 2025Review
- Estrogenic control of matrix metalloproteinases: a perspective on breast tumor invasion and metastasis.Molecular biology reports · 2025Review
- Interaction of GPER-1 with the endocrine signaling axis in breast cancer.Frontiers in endocrinology · 2025Review
- Decoding estrogen receptor and GPER biology: structural insights and therapeutic advances in ERα-positive breast cancer.Frontiers in oncology · 2025Review
- The GPR30 Receptor Is Involved in IL-6-Induced Metastatic Properties of MCF-7 Luminal Breast Cancer Cells.International journal of molecular sciences · 2024Article
- Tamoxifen resistance induction results in the upregulation of ABCG2 expression and mitoxantrone resistance in MCF-7 breast cancer cells.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- GPER: An Estrogen Receptor Key in Metastasis and Tumoral Microenvironments.International journal of molecular sciences · 2023Review
- Modulation of JAK-STAT Signaling by LNK: A Forgotten Oncogenic Pathway in Hormone Receptor-Positive Breast Cancer.International journal of molecular sciences · 2023Review
- Prediction of survival and immunotherapy response by the combined classifier of G protein-coupled receptors and tumor microenvironment in melanoma.European journal of medical research · 2023Article
- The G protein-coupled oestrogen receptor GPER in health and disease: an update.Nature reviews. Endocrinology · 2023Review
- Review
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- G Protein-Coupled Estrogen Receptor GPER: Molecular Pharmacology and Therapeutic Applications.Annual review of pharmacology and toxicology · 2023Review
- The role of the tumor microenvironment in endocrine therapy resistance in hormone receptor-positive breast cancer.Frontiers in endocrinology · 2023Review
- Comparative G-Protein-Coupled Estrogen Receptor (GPER) Systems in Diabetic and Cancer Conditions: A Review.Molecules (Basel, Switzerland) · 2022Review
- Obesity as a Risk Factor for Breast Cancer-The Role of miRNA.International journal of molecular sciences · 2022Review
- The Interplay of GPER1 with 17β-Aminoestrogens in the Regulation of the Proliferation of Cervical and Breast Cancer Cells: A Pharmacological Approach.International journal of environmental research and public health · 2022Article
- High GPER expression in triple-negative breast cancer is linked to pro-metastatic pathways and predicts poor patient outcomes.NPJ breast cancer · 2022Article
- Cytoplasmic expression of G protein-coupled estrogen receptor 1 correlates with poor postoperative prognosis in non-small cell lung cancer.Journal of thoracic disease · 2022Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionTamoxifen is widely used to treat hormone-dependent breast cancer, but its therapeutic benefit is limited by the development of drug resistance. Here, we investigated the role of estrogen G-protein coupled receptor 30 (GPR30) on Tamoxifen resistance in breast cancer.
methodsPrimary tumors (PTs) of breast cancer and corresponding metastases (MTs) were used to evaluate the expression of GPR30 and epidermal growth factor receptor (EGFR) immunohistochemically. Tamoxifen-resistant (TAM-R) subclones derived from parent MCF-7 cells were used to investigate the role of GPR30 in the development of tamoxifen resistance, using MTT assay, western blot, RT-PCR, immunofluorescence, ELISA and flow cytometry. TAM-R xenografts were established to assess anti-tumor effects of combination therapy with GPR30 antagonist G15 plus 4-hydroxytamoxifen (Tam), using tumor volume measurement and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL).
resultsIn 53 human breast cancer specimens, GPR30 expression in MTs increased compared to matched PTs; in MTs, the expression patterns of GPR30 and EGFR were closely related. Compared to parent MCF-7 cells, TAM-R cells had greater growth responses to 17β-estradiol (E2), GPR30 agonist G1 and Tam, and significantly higher activation of Mitogen-activated protein (MAP) kinases; but this increased activity was abolished by G15 or AG1478. In TAM-R cells, GPR30 cell-surface translocation facilitated crosstalk with EGFR, and reduced cAMP generation, attenuating inhibition of EGFR signaling. Combination therapy both promoted apoptosis in TAM-R cells and decreased drug-resistant tumor progression.
conclusionsLong-term endocrine treatment facilitates the translocation of GPR30 to cell surfaces, which interferes with the EGFR signaling pathway; GPR30 also attenuates the inhibition of MAP kinases. These factors contribute to tamoxifen resistance development in breast cancer. Combination therapy with GPR30 inhibitors and tamoxifen may provide a new therapeutic option for drug-resistant breast cancer.
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