ArticleThe Journal of biological chemistry2008
Switching of G-protein usage by the calcium-sensing receptor reverses its effect on parathyroid hormone-related protein secretion in normal versus malignant breast cells.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 140 citations in OpenAlex.
- Exploring multiple drug actions of a CaNaunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Cinacalcet Perturbs Membrane Permeability of bEND.3 Endothelial Cells and Suppresses Cell Proliferation.Physiological research · 2025Article
- Calcium-sensing receptor: a potential target for liver health and diseases.Journal of translational medicine · 2025Review
- Multifaceted roles of melatonin in oncology: an insight into its therapeutic potential in cancer management.Inflammopharmacology · 2025Review
- Invasion and metastasis in cancer: molecular insights and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- The calcium-sensing receptor: a comprehensive review on its role in calcium homeostasis and therapeutic implications.American journal of translational research · 2025Review
- Molecular regulation of calcium-sensing receptor (CaSR)-mediated signaling.Chronic diseases and translational medicine · 2024Review
- Article
- The ins and outs of mammary gland calcium and zinc transport: A brief review.JDS communications · 2023Review
- Calcium-Sensing Receptor (CaSR)-Mediated Intracellular Communication in Cardiovascular Diseases.Cells · 2022Review
- Vitamin D, Th17 Lymphocytes, and Breast Cancer.Cancers · 2022Review
- Calcium sensing receptor stimulates breast cancer cell migration via the Gβγ-AKT-mTORC2 signaling pathway.Journal of cell communication and signaling · 2022Article
- Ion Channels, Transporters, and Sensors Interact with the Acidic Tumor Microenvironment to Modify Cancer Progression.Reviews of physiology, biochemistry and pharmacology · 2022Review
- The bromodomain inhibitor JQ1+ reduces calcium-sensing receptor activity in pituitary cell lines.Journal of molecular endocrinology · 2021Article
- Heterogeneity of G protein activation by the calcium-sensing receptor.Journal of molecular endocrinology · 2021Article
- Therapeutic Opportunities of Targeting Allosteric Binding Sites on the Calcium-Sensing Receptor.ACS pharmacology & translational science · 2021Review
- International Union of Basic and Clinical Pharmacology. CVIII. Calcium-Sensing Receptor Nomenclature, Pharmacology, and Function.Pharmacological reviews · 2020Review
- G Protein-Coupled Receptors in Taste Physiology and Pharmacology.Frontiers in pharmacology · 2020Review
- The CaSR in Pathogenesis of Breast Cancer: A New Target for Early Stage Bone Metastases.Frontiers in oncology · 2020Review
- The calcium-sensing receptor in physiology and in calcitropic and noncalcitropic diseases.Nature reviews. Endocrinology · 2018Review
4 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
The calcium-sensing receptor (CaR) is a G-protein-coupled receptor that signals in response to extracellular calcium and regulates parathyroid hormone secretion. The CaR is also expressed on normal mammary epithelial cells (MMECs), where it has been shown to inhibit secretion of parathyroid hormone-related protein (PTHrP) and participate in the regulation of calcium and bone metabolism during lactation. In contrast to normal breast cells, the CaR has been reported to stimulate PTHrP production by breast cancer cells. In this study, we confirmed that the CaR inhibits PTHrP production by MMECs but stimulates PTHrP production by Comma-D cells (immortalized murine mammary cells) and MCF-7 human breast cancer cells. We found that changes in intracellular cAMP, but not phospholipase C or MAPK signaling, correlated with the opposing effects of the CaR on PTHrP production. Pharmacologic stimulation of cAMP accumulation increased PTHrP production by normal and transformed breast cells. Inhibition of protein kinase A activity mimicked the effects of CaR activation on inhibiting PTHrP secretion by MMECs and blocked the effects of the CaR on stimulating PTHrP production in Comma-D and MCF-7 cells. We found that the CaR coupled to Galphai in MMECs but coupled to Galphas in Comma-D and MCF-7 cells. Thus, the opposing effects of the CaR on PTHrP production are because of alternate G-protein coupling of the receptor in normal versus transformed breast cells. Because PTHrP contributes to hypercalcemia and bone metastases, switching of G-protein usage by the CaR may contribute to the pathogenesis of breast cancer.
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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.