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Best Pract Res Clin Endocrinol Metab. 2013 Jun;27(3):403-14. doi: 10.1016/j.beem.2013.02.011. Epub 2013 Mar 28.

The calcium-sensing receptor in the breast.

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Section of Endocrinology and Metabolism, Department of Internal Medicine, Yale University School of Medicine, TAC S131, Box 208020, New Haven, CT, USA.


Normal breast epithelial cells and breast cancer cells express the calcium-sensing receptor (CaSR), the master regulator of systemic calcium metabolism. During lactation, activation of the CaSR in mammary epithelial cells downregulates parathyroid hormone-related protein (PTHrP) levels in milk and in the circulation, and increases calcium transport into milk. In contrast, in breast cancer cells the CaSR upregulates PTHrP production. A switch in G-protein usage underlies the opposing effects of the CaSR on PTHrP expression in normal and malignant breast cells. During lactation, the CaSR in normal breast cells coordinates a feedback loop that matches the transport of calcium into milk and maternal calcium metabolism to the supply of calcium. A switch in CaSR G-protein usage during malignant transformation converts this feedback loop into a feed-forward cycle in breast cancer cells that may promote the growth of osteolytic skeletal metastases.


PMCA2; PTHrP; breast; lactation; mammary gland; milk; skeletal metastasis

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