Type II cyclic guanosine monophosphate-dependent protein kinase inhibits epidermal growth factor receptor activation in different cancer cell lines

Jiang,Lu; Wu,Min; Wu,Yan; Lan,Ting; Wang,Ying; Qian,Hai; Chen,Yongchang

doi:10.3892/ol.2015.3067

Type II cyclic guanosine monophosphate-dependent protein kinase inhibits epidermal growth factor receptor activation in different cancer cell lines

Authors:
- Lu Jiang
- Min Wu
- Yan Wu
- Ting Lan
- Ying Wang
- Hai Qian
- Yongchang Chen
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Affiliations: Department of Physiology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
Published online on: March 23, 2015 https://doi.org/10.3892/ol.2015.3067
Pages: 2781-2786

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Abstract

Previous data has revealed that type II cyclic guanosine monophosphate-dependent protein kinase (PKG II) inhibits epidermal growth factor (EGF)‑induced phosphorylation/activation of the epidermal growth factor receptor (EGFR) and mitogen‑activated protein kinase/extracellular‑signal‑regulated kinase (MAPK/ERK) in gastric cancer cells. The aim of the present study was to determine whether PKG II inhibited EGF‑induced phosphorylation/activation of EGFR and MAPK/ERK in cell lines derived from different cancer tissues. SW480, HepG2, OS‑RC‑2, A549, MCF‑7 and U251 cells were transfected with adenoviral constructs encoding PKG II cDNA (Ad‑PKG II) to upregulate the expression of PKG II, and then treated with 8‑(4‑chlorophenylthio)guanosine 3',5'‑cyclic monophosphate (8‑pCPT‑cGMP) in order to activate the kinase. Western blot analysis was performed to investigate the phosphorylation of EGFR and MAPK/ERK. The results demonstrated that treatment with 100 ng/ml EGF for 5 min increased the tyrosine (Tyr)1068 phosphorylation of EGFR and the threonine 202/Tyr204 phosphorylation of MAPK/ERK. Transfecting the cells with Ad‑PKG II, and stimulating the kinases with 8‑pCPT‑cGMP efficiently inhibited the EGF‑induced phosphorylation of EGFR and MAPK/ERK. The results revealed that PKG II had an inhibitory effect upon EGFR activation and the consequent MAPK/ERK-mediated signaling of cell lines derived from the various cancer tissues.

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