Calcium-sensing receptor in breast physiology and cancer
The calcium-sensing receptor (CaSR) is expressed in normal breast epithelial cells and in breast cancer cells. During lactation, activation of the CaSR in mammary epithelial cells increases calcium transport into milk and inhibits parathyroid hormone-related protein (PTHrP) secretion into milk and i...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-09-01
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| Series: | Frontiers in Physiology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00440/full |
| _version_ | 1819212454196936704 |
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| author | Wonnam Kim John J Wysolmerski |
| author_facet | Wonnam Kim John J Wysolmerski |
| author_sort | Wonnam Kim |
| collection | DOAJ |
| description | The calcium-sensing receptor (CaSR) is expressed in normal breast epithelial cells and in breast cancer cells. During lactation, activation of the CaSR in mammary epithelial cells increases calcium transport into milk and inhibits parathyroid hormone-related protein (PTHrP) secretion into milk and into the circulation. The ability to sense changes in extracellular calcium allows the lactating breast to actively participate in the regulation of systemic calcium and bone metabolism, and to coordinate calcium usage with calcium availability during milk production. Interestingly, as compared to normal breast cells, in breast cancer cells, the regulation of PTHrP secretion by the CaSR becomes rewired due to a switch in its G-protein usage such that activation of the CaSR increases instead of decreases PTHrP production. In normal cells the CaSR couples to Gi to inhibit cAMP and PTHrP production, whereas in breast cancer cells, it couples to Gs to stimulate cAMP and PTHrP production. Activation of the CaSR on breast cancer cells regulates breast cancer cell proliferation, death and migration, in part, by stimulating PTHrP production. In this article, we discuss the biology of the CaSR in the normal breast and in breast cancer, and review recent findings suggesting that the CaSR activates a nuclear pathway of PTHrP action that stimulates cellular proliferation and inhibits cell death, helping cancer cells adapt to elevated extracellular calcium levels. Understanding the diverse actions mediated by the CaSR may help us better understand lactation physiology, breast cancer progression and osteolytic bone metastases. |
| first_indexed | 2024-12-23T06:43:13Z |
| format | Article |
| id | doaj.art-70e3a03aae0a4cc49789bef36ad1d940 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-23T06:43:13Z |
| publishDate | 2016-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-70e3a03aae0a4cc49789bef36ad1d9402022-12-21T17:56:39ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2016-09-01710.3389/fphys.2016.00440214879Calcium-sensing receptor in breast physiology and cancerWonnam Kim0John J Wysolmerski1Yale University School of MedicineYale University School of MedicineThe calcium-sensing receptor (CaSR) is expressed in normal breast epithelial cells and in breast cancer cells. During lactation, activation of the CaSR in mammary epithelial cells increases calcium transport into milk and inhibits parathyroid hormone-related protein (PTHrP) secretion into milk and into the circulation. The ability to sense changes in extracellular calcium allows the lactating breast to actively participate in the regulation of systemic calcium and bone metabolism, and to coordinate calcium usage with calcium availability during milk production. Interestingly, as compared to normal breast cells, in breast cancer cells, the regulation of PTHrP secretion by the CaSR becomes rewired due to a switch in its G-protein usage such that activation of the CaSR increases instead of decreases PTHrP production. In normal cells the CaSR couples to Gi to inhibit cAMP and PTHrP production, whereas in breast cancer cells, it couples to Gs to stimulate cAMP and PTHrP production. Activation of the CaSR on breast cancer cells regulates breast cancer cell proliferation, death and migration, in part, by stimulating PTHrP production. In this article, we discuss the biology of the CaSR in the normal breast and in breast cancer, and review recent findings suggesting that the CaSR activates a nuclear pathway of PTHrP action that stimulates cellular proliferation and inhibits cell death, helping cancer cells adapt to elevated extracellular calcium levels. Understanding the diverse actions mediated by the CaSR may help us better understand lactation physiology, breast cancer progression and osteolytic bone metastases.http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00440/fullLactationParathyroid Hormone-Related Proteinbreast cancermammary glandcalcium-sensing receptor |
| spellingShingle | Wonnam Kim John J Wysolmerski Calcium-sensing receptor in breast physiology and cancer Frontiers in Physiology Lactation Parathyroid Hormone-Related Protein breast cancer mammary gland calcium-sensing receptor |
| title | Calcium-sensing receptor in breast physiology and cancer |
| title_full | Calcium-sensing receptor in breast physiology and cancer |
| title_fullStr | Calcium-sensing receptor in breast physiology and cancer |
| title_full_unstemmed | Calcium-sensing receptor in breast physiology and cancer |
| title_short | Calcium-sensing receptor in breast physiology and cancer |
| title_sort | calcium sensing receptor in breast physiology and cancer |
| topic | Lactation Parathyroid Hormone-Related Protein breast cancer mammary gland calcium-sensing receptor |
| url | http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00440/full |
| work_keys_str_mv | AT wonnamkim calciumsensingreceptorinbreastphysiologyandcancer AT johnjwysolmerski calciumsensingreceptorinbreastphysiologyandcancer |