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Article

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
  • View Affiliations / Copyright

    Affiliations: School of Medical Science and Laboratory Medicine, Jiangsu University, Jiangsu 212013, P.R. China
  • Pages: 1190-1194
    |
    Published online on: August 27, 2012
       https://doi.org/10.3892/mmr.2012.1050
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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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Copy and paste a formatted citation
Spandidos Publications style
Sang J, Chen Y, Jiang L, Tao Y, Wu Y, Wang Y, Li Y, Lan T and Shao G: Type II cGMP-dependent protein kinase inhibits ERK/JNK-mediated activation of transcription factors in gastric cancer cells. Mol Med Rep 6: 1190-1194, 2012.
APA
Sang, J., Chen, Y., Jiang, L., Tao, Y., Wu, Y., Wang, Y. ... Shao, G. (2012). Type II cGMP-dependent protein kinase inhibits ERK/JNK-mediated activation of transcription factors in gastric cancer cells. Molecular Medicine Reports, 6, 1190-1194. https://doi.org/10.3892/mmr.2012.1050
MLA
Sang, J., Chen, Y., Jiang, L., Tao, Y., Wu, Y., Wang, Y., Li, Y., Lan, T., Shao, G."Type II cGMP-dependent protein kinase inhibits ERK/JNK-mediated activation of transcription factors in gastric cancer cells". Molecular Medicine Reports 6.5 (2012): 1190-1194.
Chicago
Sang, J., Chen, Y., Jiang, L., Tao, Y., Wu, Y., Wang, Y., Li, Y., Lan, T., Shao, G."Type II cGMP-dependent protein kinase inhibits ERK/JNK-mediated activation of transcription factors in gastric cancer cells". Molecular Medicine Reports 6, no. 5 (2012): 1190-1194. https://doi.org/10.3892/mmr.2012.1050
Copy and paste a formatted citation
x
Spandidos Publications style
Sang J, Chen Y, Jiang L, Tao Y, Wu Y, Wang Y, Li Y, Lan T and Shao G: Type II cGMP-dependent protein kinase inhibits ERK/JNK-mediated activation of transcription factors in gastric cancer cells. Mol Med Rep 6: 1190-1194, 2012.
APA
Sang, J., Chen, Y., Jiang, L., Tao, Y., Wu, Y., Wang, Y. ... Shao, G. (2012). Type II cGMP-dependent protein kinase inhibits ERK/JNK-mediated activation of transcription factors in gastric cancer cells. Molecular Medicine Reports, 6, 1190-1194. https://doi.org/10.3892/mmr.2012.1050
MLA
Sang, J., Chen, Y., Jiang, L., Tao, Y., Wu, Y., Wang, Y., Li, Y., Lan, T., Shao, G."Type II cGMP-dependent protein kinase inhibits ERK/JNK-mediated activation of transcription factors in gastric cancer cells". Molecular Medicine Reports 6.5 (2012): 1190-1194.
Chicago
Sang, J., Chen, Y., Jiang, L., Tao, Y., Wu, Y., Wang, Y., Li, Y., Lan, T., Shao, G."Type II cGMP-dependent protein kinase inhibits ERK/JNK-mediated activation of transcription factors in gastric cancer cells". Molecular Medicine Reports 6, no. 5 (2012): 1190-1194. https://doi.org/10.3892/mmr.2012.1050
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