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Article

Type II cGMP‑dependent protein kinase inhibits epidermal growth factor‑induced phosphatidylinositol‑3‑kinase/Akt signal transduction in gastric cancer cells

  • Authors:
    • Min Wu
    • Yongchang Chen
    • Lu Jiang
    • Yueying Li
    • Ting Lan
    • Ying Wang
    • Hai Qian
  • View Affiliations / Copyright

    Affiliations: Department of Physiology, School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
  • Pages: 1723-1728
    |
    Published online on: October 15, 2013
       https://doi.org/10.3892/ol.2013.1630
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Abstract

Our previous study revealed that Type II cGMP‑dependent protein kinase (PKG II) inhibits epidermal growth factor (EGF)‑induced MAPK/ERK and MAPK/JNK‑mediated signal transduction through the inhibition of the phosphorylation/activation of the EGF receptor (EGFR). As EGFR also mediates several other signal transduction pathways besides MAPK‑mediated pathways, the present study was designed to investigate whether PKG II was able to inhibit EGF/EGFR‑induced phosphatidylinositol‑3‑kinase (PI3K)/Akt‑mediated signal transduction. The AGS human gastric cancer cell line was infected with adenoviral constructs encoding a cDNA of PKG II (Ad‑PKG II) to increase the expression of PKG II, and treated with 8‑pCPT‑cGMP to activate the enzyme. Western blotting was used to detect the phosphorylation/activation of the key components of the signal transduction pathway, including EGFR, PI3K, Akt, mTOR and NF‑κB. The levels of apoptosis‑related proteins, including Bax, Bcl‑2, caspase 9 and DNA fragment factor (DFF), were also determined by western blotting. Terminal deoxynucleotidyl transferase‑mediated dUTP nick end‑labeling staining was used to detect the apoptosis of the AGS cells. The results revealed that EGF treatment increased the phosphorylation (activation) of EGFR, PI3K, Akt and mTOR, and increased the nuclear localization (activation) of NF‑κB. EGF treatment also reduced the apoptosis of the AGS cells and increased the expression of the anti‑apoptotic protein, Bcl‑2, but had no effect on the expression of the pro‑apoptotic protein, Bax, and did not alter the levels of caspase 9 and DFF. Increasing the PKG II activity of AGS cells by infecting them with Ad‑PKG II and stimulating them with 8‑pCPT‑cGMP inhibited the EGF‑induced activation of EGFR, PI3K, Akt, mTOR and NF‑κB; caused an increase in caspase 9 breakdown (activation) and DFF levels; and reversed the anti‑apoptotic effect of EGF. The results suggest that PKG II may also inhibit EGF‑induced signal transduction of PI3K/Akt‑mediated pathways, and further confirm that PKG II is able to block the activation of EGFR.
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1 

Marone R, Cmiljanovic V, Giese B and Wymann MP: Targeting phosphoinositide 3-kinase: moving towards therapy. Biochem Biophys Acta. 1784:159–185. 2008.PubMed/NCBI

2 

Song G, Ouyang G and Bao S: The activation of Akt/PKB signaling pathway and cell survival. J Cell Mol Med. 9:59–71. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Edward LA, Thiesen B, Dragowska WH, et al: Inhibiton of ILK in PTEN-mutant human glioblastomas inhibits PKB/Akt activation, induces apoptosis and delays tumor growth. Oncogene. 24:3596–3605. 2005. View Article : Google Scholar : PubMed/NCBI

4 

Berg M and Soreide K: EGFR and downstream genetic alterations in KRAS/BRAF and PI3K/AKT pathways in colorectal cancer: implications for targeted therapy. Discov Med. 14:207–214. 2012.PubMed/NCBI

5 

Osaki M, Oshimura M and Ito H: PI3K-Akt pathway: its functions and alteration in human cancer. Apoptosis. 9:667–676. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Orstavik S, Natarajan V, Taskén K, et al: Characterization of the human gene encoding the type I alpha and type I beta cGMP-dependent protein kinase (PRKG1). Genomics. 42:311–318. 1997. View Article : Google Scholar : PubMed/NCBI

7 

Orstavik S, Solberg R, Taskén K, et al: Molecular cloning, cDNA structure and chromosomal localization of the human type II cGMP-dependent protein kinase. Biochem Biophys Res Commun. 220:759–765. 1996. View Article : Google Scholar : PubMed/NCBI

8 

Browing DD: Protein kinase G as a therapeutic target for the treatment of metastatic colorectal cancer. Expert Opin Ther Targets. 12:367–376. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Yang SQ, Chen YC, Wang Y, et al: Expression of cGMP dependent protein kinase II in cancer cell lines was obviously decreased. J Jiangsu Univ (Medicine Edition). 18:1–5. 2008.

10 

Chen YC, Ren F, Sang JR, et al: Type II cGMP-dependent protein kinase inhibits proliferation of the gastric cancer cell line BGC-823. Mol Med Rep. 3:361–366. 2010.PubMed/NCBI

11 

Wu Y, Chen Y, Qu R, et al: Type II cGMP-dependent protein kinase inhibits EGF-triggered signal transduction of the MAPK/ERK-mediated pathway in gastric cancer cells. Oncol Rep. 27:553–558. 2012.PubMed/NCBI

12 

Lan T, Chen Y, Sang J, et al: Type II cGMP-dependent protein kinase inhibits EGF-induced MAPK/JNK signal transduction in breast cancer cells. Oncol Rep. 27:2039–2044. 2012.PubMed/NCBI

13 

Dong P, Xu Z, Jia N, et al: Elevated expression of p53 gain-of-function mutation R175H in endometrial cancer cells can increase the invasive phenotypes by activation of the EGFR/PI3K/AKT pathway. Mol Cancer. 8:1032009. View Article : Google Scholar : PubMed/NCBI

14 

Quesnelle KM, Boehm AL and Grandis JR: STAT-mediated EGFR signaling in cancer. J Cell Biochem. 102:311–319. 2007. View Article : Google Scholar : PubMed/NCBI

15 

Hofmann F: The biology of cyclic GMP-dependent protein kinases. J Biol Chem. 280:1–4. 2005. View Article : Google Scholar : PubMed/NCBI

16 

Nie HG, Chen L, Han DY, et al: Regulation of epithelial sodium channels by cGMP/PKGII. J Physiol. 587:2663–2676. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Rangaswami H, Marathe N, Zhuang S, et al: Type II cGMP-dependent protein kinase mediates osteoblast mechanotransduction. J Biol Chem. 284:14796–14808. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Rangaswami H, Schwappacher R, Marathe N, et al: Cyclic GMP and protein kinase G control a Src-containing mechanosome in osteoblasts. Sci Signal. 3:ra912010.PubMed/NCBI

19 

Cook AL and Haynes JM: Protein kinase G II-mediated proliferative effects in human cultured prostatic stromal cells. Cell Signal. 16:253–261. 2004. View Article : Google Scholar : PubMed/NCBI

20 

Swartling FJ, Ferletta M, Kastemar M, et al: Cyclic GMP-dependent protein kinase II inhibits cell proliferation, Sox9 expression and Akt phosphorylation in human glioma cell lines. Oncogene. 28:3121–3131. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Fallahian F, Karami-Tehrani F, Salami S and Aghaei M: Cyclic GMP induced apoptosis via protein kinase G in oestrogen receptor-positive and -negative breast cancer cell lines. FEBS J. 278:3360–3369. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Xie Z, Peng J, Pennypacker SD and Chen Y: Critical role for the catalytic activity of phospholipase C-γ1 in epidermal growth factor-induced cell migration. Biochem Biophys Res Commun. 399:425–428. 2010.

23 

Yap TA, Garrett MD, Walton MI, et al: Targeting the PI3K-AKT-mTOR pathway: progress, pitfalls, and promises. Curr Opin Pharmacol. 8:393–412. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Normanno N, Bianco C, De Luca A, et al: Target-based agents against ErbB receptors and their ligands: a novel approach to cancer treatment. Endocr Relat Cancer. 10:1–21. 2003. View Article : Google Scholar : PubMed/NCBI

25 

Sharma SV, Bell DW, Settleman J and Haber DA: Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer. 7:169–181. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Hynes NE and MacDonald G: ErbB receptors and signaling pathways in cancer. Curr Opin Cell Biol. 21:177–184. 2009. View Article : Google Scholar : PubMed/NCBI

27 

Quatrale AE, Porcelli L, Silvestris N, et al: EGFR tyrosine kinases inhibitors in cancer treatment: in vitro and in vivo evidence. Front Biosci. 16:1962–1972. 2011. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Wu M, Chen Y, Jiang L, Li Y, Lan T, Wang Y and Qian H: Type II cGMP‑dependent protein kinase inhibits epidermal growth factor‑induced phosphatidylinositol‑3‑kinase/Akt signal transduction in gastric cancer cells. Oncol Lett 6: 1723-1728, 2013.
APA
Wu, M., Chen, Y., Jiang, L., Li, Y., Lan, T., Wang, Y., & Qian, H. (2013). Type II cGMP‑dependent protein kinase inhibits epidermal growth factor‑induced phosphatidylinositol‑3‑kinase/Akt signal transduction in gastric cancer cells. Oncology Letters, 6, 1723-1728. https://doi.org/10.3892/ol.2013.1630
MLA
Wu, M., Chen, Y., Jiang, L., Li, Y., Lan, T., Wang, Y., Qian, H."Type II cGMP‑dependent protein kinase inhibits epidermal growth factor‑induced phosphatidylinositol‑3‑kinase/Akt signal transduction in gastric cancer cells". Oncology Letters 6.6 (2013): 1723-1728.
Chicago
Wu, M., Chen, Y., Jiang, L., Li, Y., Lan, T., Wang, Y., Qian, H."Type II cGMP‑dependent protein kinase inhibits epidermal growth factor‑induced phosphatidylinositol‑3‑kinase/Akt signal transduction in gastric cancer cells". Oncology Letters 6, no. 6 (2013): 1723-1728. https://doi.org/10.3892/ol.2013.1630
Copy and paste a formatted citation
x
Spandidos Publications style
Wu M, Chen Y, Jiang L, Li Y, Lan T, Wang Y and Qian H: Type II cGMP‑dependent protein kinase inhibits epidermal growth factor‑induced phosphatidylinositol‑3‑kinase/Akt signal transduction in gastric cancer cells. Oncol Lett 6: 1723-1728, 2013.
APA
Wu, M., Chen, Y., Jiang, L., Li, Y., Lan, T., Wang, Y., & Qian, H. (2013). Type II cGMP‑dependent protein kinase inhibits epidermal growth factor‑induced phosphatidylinositol‑3‑kinase/Akt signal transduction in gastric cancer cells. Oncology Letters, 6, 1723-1728. https://doi.org/10.3892/ol.2013.1630
MLA
Wu, M., Chen, Y., Jiang, L., Li, Y., Lan, T., Wang, Y., Qian, H."Type II cGMP‑dependent protein kinase inhibits epidermal growth factor‑induced phosphatidylinositol‑3‑kinase/Akt signal transduction in gastric cancer cells". Oncology Letters 6.6 (2013): 1723-1728.
Chicago
Wu, M., Chen, Y., Jiang, L., Li, Y., Lan, T., Wang, Y., Qian, H."Type II cGMP‑dependent protein kinase inhibits epidermal growth factor‑induced phosphatidylinositol‑3‑kinase/Akt signal transduction in gastric cancer cells". Oncology Letters 6, no. 6 (2013): 1723-1728. https://doi.org/10.3892/ol.2013.1630
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