Calcium-Sensing Receptor in Breast Physiology and Cancer
نویسندگان
چکیده
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 Gαi to inhibit cAMP and PTHrP production, whereas in breast cancer cells, it couples to Gαs 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.
منابع مشابه
A genetic polymorphism (rs17251221) in the calcium-sensing receptor is associated with breast cancer susceptibility and prognosis.
BACKGROUND Calcium-sensing receptor (CaSR) is a typical G protein coupled receptor. The rs17251221 SNP is located in an intron of the CaSR gene, and the G allele is considered a gain of function mutation. Previous studies revealed that rs17251221 polymorphisms contribute to the risk of developing certain types of cancers. This study investigated the rs17251221 SNP in breast cancer by analyzing ...
متن کاملThe cytotoxic effect of memantine and its effect on cytoskeletal proteins expression in metastatic breast cancer cell line
Objective(s):Breast cancer is an important leading cause of death from cancer. Stathmin and tau proteins are regulators of cell motility, and their overexpression is associated with the progression and bad prognosis of breast cancer. Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is the potential inhibitor of tau protein in neurons. This study determines the effect of memantine ...
متن کاملRelation between Estrogen and Progesterone Receptor Status with p53, Ki67 and Her-2 Markers in Patients with Breast Cancer
Background: Breast cancer is the most common cancer in women, containing approximately one third of all illnesses in women. Assessment of molecular markers is valuable in predicting the outcome of disease and decision making for optimal treatment. The purpose of this study was to determine the relationship between estrogen and progesterone receptors with Her-2, Ki67, P53, and clinicopathologica...
متن کاملExtracellular signal-regulated kinases 1 and 2 and TRPC1 channels are required for calcium-sensing receptor-stimulated MCF-7 breast cancer cell proliferation.
The calcium-sensing receptor (CaR), is a G protein-dependent receptor that responds to increments in extracellular Ca(2+) ([Ca(2+)](o)). We previously reported that an increase in [Ca(2+)](o) induced a release of intracellular calcium and Ca(2+) entry via store operated channels (SOCs). We also demonstrated that MCF-7 cells express Transient Receptor Potential canonical 1 (TRPC1) channels. Here...
متن کامل