Mitogen-activated protein kinase cascade in human normal and tumoral parathyroid cells

The calcium-sensing receptor (CaR) activation has recently been shown to modulate the ERK1 and ERK2 cascade in different cell lines. The present study investigated this pathway in human normal and tumoral parathyroid cells. In cells from normal parathyroids and almost all hyperplasia increasing extracellular calcium concentrations (Cao2+) induced a significant activation of ERK1 and -2, the percent stimulation over basal activity (at 0.5 mm Cao2+) being 545 ± 140 and 800 ± 205 in normal cells and 290 ± 71 and 350 ± 73 in hyperplasia at 1 and 2 mm Cao2+, respectively. This effect was mediated by CaR because it was mimicked by the receptor agonist gadolinium and neomycin. Basal and Cao2+-stimulated ERK1 and -2 activity was nearly abolished by the PKC inhibitor calphostin C, and PKA changes did not affect ERK1 and -2 activity. PI3K blockade by wortmannin, known to prevent G protein βγ subunit effect on ERK1 and -2, induced a 30% reduction of the Cao2+-stimulated ERK1 and -2 activity. Adenomatous cells showed...