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

S. Corbetta, A. Lania, M. Filopanti, L. Vicentini, E. Ballaré, A. Spada

Research output: Contribution to journalArticlepeer-review


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 (Cao 2+) induced a significant activation of ERK1 and -2, the percent stimulation over basal activity (at 0.5 mM Cao 2+) being 545 ± 140 and 800 ± 205 in normal cells and 290 ± 71 and 350 ± 73 in hyperplasia at 1 and 2 mM Cao 2+, respectively. This effect was mediated by CaR because it was mimicked by the receptor agonist gadolinium and neomycin. Basal and Cao 2+-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 Cao 2+-stimulated ERK1 and -2 activity. Adenomatous cells showed high PKC-dependent ERK1 and -2 activity in resting conditions that was unresponsive to high Cao 2+. A role of MAPK on PTH secretion was suggested by the finding that PD98059, a specific MEK inhibitor, abolished the inhibitory effect of 1.5 mM Cao 2+ on PTH release from normal parathyroid cells. In conclusion, these data first demonstrate that CaR activation, through the PKC pathway and, to a lesser extent, PI3K, increases ERK1 and -2 activity in normal parathyroid cells and this cascade seems to be involved in the modulation of PTH secretion by Cao 2+. Interestingly, this signaling pathway is disrupted in parathyroid tumors.

Original languageEnglish
Pages (from-to)2201-2205
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Issue number5
Publication statusPublished - 2002

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism


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