Type II, but not type I, cGMP-dependent protein kinase reverses bFGF-induced proliferation and migration of U251 human glioma cells

Cao,Zhi-Hong; Tao,Yan; Sang,Jian-Rong; Gu,Yin-Jie; Bian,Xiu-Juan; Chen,Yong-Chang

doi:10.3892/mmr.2013.1319

Type II, but not type I, cGMP-dependent protein kinase reverses bFGF-induced proliferation and migration of U251 human glioma cells

Authors:
- Zhi-Hong Cao
- Yan Tao
- Jian-Rong Sang
- Yin-Jie Gu
- Xiu-Juan Bian
- Yong-Chang Chen
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Affiliations: Department of Intensive Care Unit, Affiliated Hospital of Jiangsu University, Yixing, Jiangsu 214200, P.R. China, School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China, Department of Respiratory Diseases, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China
Published online on: February 11, 2013 https://doi.org/10.3892/mmr.2013.1319
Pages: 1229-1234

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Abstract

Previous data have shown that the type II cGMP‑dependent protein kinase (PKG II) inhibits the EGF‑induced MAPK signaling pathway. In order to thoroughly investigate PKG, it is necessary to elucidate the function of another type of PKG, PKG I. The aim of this study was to investigate the possible inhibitory effect of PKG II and PKG I activity on the basic fibroblast growth factor (bFGF)‑induced proliferation and migration of U251 human glioma cells and the possible underlying mechanisms. U251 cells were infected with adenoviral constructs encoding cDNA of PKG I (Ad‑PKG I) or PKG II (Ad‑PKG II) to increase the expression levels of PKG I or PKG II and then treated with 8‑Br‑cGMP and 8‑pCPT‑cGMP, respectively, to activate the enzyme. An MTT assay was used to detect the proliferation of the U251 cells. The migration of the U251 cells was analyzed using a Transwell migration assay. Western blot analysis was used to detect the phosphorylation/activation of the fibroblast growth factor receptor (FGFR), MEK and ERK and the nuclear distribution of p-ERK. The results showed that bFGF treatment increased the proliferation and migration of U251 cells, accompanied by increased phosphorylation of FGFR, MEK and ERK. Furthermore, the nuclear distribution of p-ERK increased following bFGF treatment. Increasing the activity of PKG II through infection with Ad-PKG II and stimulation with 8-pCPT-cGMP significantly attenuated the aforementioned effects of the bFGF treatment, while increased PKG I activity did not inhibit the effects of bFGF treatment. These data suggest that increased PKG II activity attenuates bFGF‑induced proliferation and migration by inhibiting the MAPK/ERK signaling pathway, whereas PKG I does not.

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