Regulation of mammary tight junctions through parathyroid hormone-related peptide-induced activation of apical calcium channels.

Tight junctions (TJs) play an essential role in cell-cell contact between mammary epithelial cells and, as such, play a critical role in cell function. Moreover, calcium (Ca) plays a crucial role in the formation and maintenance of mammary TJs. Given that parathyroid hormone-related peptide (PTHrP) is involved in cellular Ca homeostasis, we postulated a role for PTHrP in the regulation of mammary TJs. The effect of PTHrP(1-34) on TJs was studied in the mouse mammary cell line COMMA-1D by measuring transepithelial electrical resistance across cell monolayers and measuring the expression of TJ proteins. PTHrP stimulated TJ formation but only under conditions where extracellular Ca was limiting. This effect of PTHrP appeared to be indirect and mediated via increased intracellular availability of Ca as a result of increased Ca-channel activity in the apical membrane. The changes in TJs were associated with altered expression of the TJ protein occludin, but expression of the TJ protein claudin-1 was not affected. The effects of PTHrP on mammary TJs are independent of prolactin. In conclusion, PTHrP enhances mammary TJ formation when extracellular Ca is limiting by maintaining intracellular Ca supplies.