title: The calcium-sensing receptor in the breast.
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.
authors.affiliation: 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
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Vanhouten
authors.forename: John J
authors.initials: JJ
authors.lastname: Wysolmerski
mesh_terms: D000818:Animals; D001940:Breast / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D007774:Lactation / Q000378:metabolism*; D008321:Mammary Glands, Animal / Q000378:metabolism; D042361:Mammary Glands, Human / Q000378:metabolism*; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism; D044169:Receptors, Calcium-Sensing / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D044162:Parathyroid Hormone-Related Protein; D044169:Receptors, Calcium-Sensing
keywords: PMCA2; PTHrP; breast; lactation; mammary gland; milk; skeletal metastasis