TY - JOUR
T1 - High calcium activates the EGF receptor potentially through the calcium-sensing receptor in Leydig cancer cells
AU - Tfelt-Hansen, Jacob
AU - Yano, Shozo
AU - MacLeod, R. John
AU - Smajilovic, Sanela
AU - Chattopadhyay, Naibedya
AU - Brown, Edward M.
PY - 2005/6/1
Y1 - 2005/6/1
N2 - 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.
AB - 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.
KW - Calcium-sensing receptor
KW - Epidermal growth factor receptor
KW - Humoral hypercalcemia
KW - Leydig cancer
KW - Transactivation
UR - http://www.scopus.com/inward/record.url?scp=24944544464&partnerID=8YFLogxK
U2 - 10.1080/08977190500126272
DO - 10.1080/08977190500126272
M3 - Journal article
C2 - 16019433
AN - SCOPUS:24944544464
SN - 0897-7194
VL - 23
SP - 117
EP - 123
JO - Growth Factors
JF - Growth Factors
IS - 2
ER -
