Type II cGMP-dependent protein kinase inhibits ERK/JNK-mediated activation of transcription factors in gastric cancer cells

Sang,Jianrong; Chen,Yongchang; Jiang,Lu; Tao,Yan; Wu,Yan; Wang,Ying; Li,Yueying; Lan,Ting; Shao,Genbao

doi:10.3892/mmr.2012.1050

Type II cGMP-dependent protein kinase inhibits ERK/JNK-mediated activation of transcription factors in gastric cancer cells

Authors:
- Jianrong Sang
- Yongchang Chen
- Lu Jiang
- Yan Tao
- Yan Wu
- Ying Wang
- Yueying Li
- Ting Lan
- Genbao Shao
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Affiliations: School of Medical Science and Laboratory Medicine, Jiangsu University, Jiangsu 212013, P.R. China
Published online on: August 27, 2012 https://doi.org/10.3892/mmr.2012.1050
Pages: 1190-1194

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Abstract

A previous study has shown that type II cGMP‑dependent protein kinase (PKG II) inhibits the proliferation of gastric cancer cells through blocking EGF-triggered MAPK/ERK signal transduction, indicating that the kinase may be a potential anticancer factor. In the present study, the role of PKG II in the EGF-induced activation of transcription factors in the MAPK/ERK signal transduction pathway was investigated. BGC-823 human gastric cancer cells were infected with adenoviral constructs encoding the cDNA of PKG II (pAd‑PKG II) to increase the expression of PKG II and treated with 8-pCPT‑cGMP to activate the enzyme. Using luciferase reporter assays, it was revealed that PKG II markedly suppressed the EGF-induced transcriptional activities of AP-1 and Elk1. Consistent with the inhibitory effect of PKG II on AP-1 activity, the expression levels of c-Jun and c-Fos, components of AP-1, were also inhibited. Co-immunoprecipitation analysis demonstrated that EGF treatment increased the AP-1 content through inducing the formation of p-c-Jun-c-Jun homodimers and p-c-Jun-c-Fos heterodimers. However, this combination was efficiently blocked by activated PKG II. While pretreatments with MAPK inhibitors suppressed the EGF-induced transcriptional activities of AP-1 and Elk1, PKG II prevented the EGF-induced phosphorylation/activation of ERK and JNK, but not the phosphorylation of p38MAPK induced by EGF. These data suggest that PKG II inhibits the EGF-triggered proliferation of gastric cancer cells through suppressing ERK-/JNK-, but not p38MAPK, -mediated AP-1 and Elk1 transactivation.

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