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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.

Author information

1
Section of Endocrinology and Metabolism, Department of Internal Medicine, Yale University School of Medicine, TAC S131, Box 208020, New Haven, CT, USA. joshua.vanhouten@yale.edu

Abstract

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.

KEYWORDS:

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

PMID:
23856268
PMCID:
PMC3713417
DOI:
10.1016/j.beem.2013.02.011
[Indexed for MEDLINE]
Free PMC Article

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