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High calcium activates the EGF receptor potentially through the calcium-sensing receptor in Leydig cancer cells

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  • Tfelt, Jacob
  • Shozo Yano
  • R. John MacLeod
  • Sanela Smajilovic
  • Naibedya Chattopadhyay
  • Edward M. Brown

Epidermal growth factor (EGF) plays an important role in the physiology and pathophysiology of the Leydig cell. In H-500 rat Leydig cancer cells, a model for humoral hypercalcemia of malignancy (HHM), we previously showed that the calcium-sensing receptor (CaR) stimulates PTHrP release and proliferation, both involving multiple mitogen-activated protein kinases. An emerging concept of signaling by G-protein coupled receptors (GPCR) is that it occurs via transactivation of receptor tyrosine kinases. Therefore, we investigated whether stimulation with calcium activates the EGFR in H-500 Leydig cancer cells. We show that treatment of H-500 cells with Ca2+ results in EGFR phosphorylation. The CaR-induced activation of ERK1/2, induction of PTHrP release and stimulation of cellular proliferation in H-500 cells are likewise mediated, in large part, through the EGFR. In conclusion, the calcium activates the EGFR, possibly through the CaR, to regulate downstream signaling events and important biological functions in a model of HHM.

OriginalsprogEngelsk
TidsskriftGrowth Factors
Vol/bind23
Udgave nummer2
Sider (fra-til)117-123
Antal sider7
ISSN0897-7194
DOI
StatusUdgivet - 1 jun. 2005
Eksternt udgivetJa

ID: 203876603