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

Jacob Tfelt-Hansen; Shozo Yano; R. John MacLeod; Sanela Smajilovic; Naibedya Chattopadhyay; Edward M. Brown

doi:10.1080/08977190500126272

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

Jacob Tfelt-Hansen^*, Shozo Yano, R. John MacLeod, Sanela Smajilovic, Naibedya Chattopadhyay, Edward M. Brown

^*Corresponding author for this work

29 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Growth Factors
Volume	23
Issue number	2
Pages (from-to)	117-123
Number of pages	7
ISSN	0897-7194
DOIs	https://doi.org/10.1080/08977190500126272
Publication status	Published - 1 Jun 2005
Externally published	Yes

Keywords

Calcium-sensing receptor
Epidermal growth factor receptor
Humoral hypercalcemia
Leydig cancer
Transactivation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1080/08977190500126272

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title = "High calcium activates the EGF receptor potentially through the calcium-sensing receptor in Leydig cancer cells",

abstract = "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.",

keywords = "Calcium-sensing receptor, Epidermal growth factor receptor, Humoral hypercalcemia, Leydig cancer, Transactivation",

author = "Jacob Tfelt-Hansen and Shozo Yano and MacLeod, {R. John} and Sanela Smajilovic and Naibedya Chattopadhyay and Brown, {Edward M.}",

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doi = "10.1080/08977190500126272",

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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

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ER -

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

Abstract

Keywords

UN SDGs

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