Protein Kinase B Phosphorylation Correlates with Vascular Endothelial Growth Factor A and Microvessel Density in Gastric Adenocarcinoma

Zhou, Xiaodong; Chen, H X; Guan, Run-Nian; Lei, Yifeng; Shu, Xiao Zheng; Zhu, Yin; Lv, Nonghua

doi:10.1177/030006051204000610

Cited by 9 publications

(7 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[ 12 - 14 ]. Our previous study confirmed that p-Akt involved in angiogenesis of gastric adenocarcinoma and Akt activation may contribute to angiogenesis via VEGF-A up-regulation [ 15 ]. In this study, the positive staining rates of p-Akt and p-mTOR in 55 cases of gastric cancer were 74.54% and 85.45% respectively.…”

Section: Discussionsupporting

confidence: 70%

Lymphangiogenesis in Gastric Cancer regulated through Akt/mTOR-VEGF-C/VEGF-D axis

et al. 2015

View full text Add to dashboard Cite

BackgroundLymphangiogenesis plays a significant role in metastasis and recurrence of gastric cancer. There is no report yet focusing on the modulation of VEGF pathway and lymphangiogenesis of gastric cancer by targeting Akt/mTOR pathway. This study aims to demonstrate the relationship between Akt/mTOR pathway and VEGF-C/-D in gastric cancer.MethodsWe collected surgically resected gastric adenocarcinoma specimens from 55 consented patients. Immunohistochemistry staining of p-Akt, p-mTOR, VEGF-C, VEGF-D were performed and scored by two independent pathologists. The results were presented as staining intensity and positive staining cell rate. We also measured lymphatic vessel density (LVD) by D2-40 staining. Different dosages of p-Akt inhibitor LY294002 (12.5 μM, 25 μM, 50 μM) and p-mTOR inhibitor Rapamycin (25 nM, 50 nM, 100 nM) were given to gastric cancer cell line SGC-7901 in vitro. The inhibition rate of cell growth was tested by MTT at 24 h, 48 h and 72 h, respectively and protein expressions of Akt, p-Akt, mTOR, p-mTOR, VEGF-C and VEGF-D were examined by Western blot.ResultsThe positive staining rates of p-Akt, p-mTOR, VEGF-C and VEGF-D in 55 gastric cancer clinical specimens were 74.54%, 85.45%, 72.73% and 58.18%. p-Akt and p-mTOR were positively correlated with VEGF-C and VEGF-D (p < 0.01). The LVD increased with incremental tendency of staining intensity of p-Akt, p-mTOR, VEGF-C and VEGF-D. LY294002 or Rapamycin significantly suppressed SGC-7901 cell growth and the inhibition rate was dose and time dependent (p < 0.001). In addition, the protein expression of p-Akt and p-mTOR were positively correlated with that of VEGF-C and VEGF-D (p < 0.05).ConclusionsThe level of LVD in gastric cancer specimens was significant higher than that of normal gastric tissue and was positively correlated with p-Akt, p-mTOR, VEGF-C and VEGF-D. Inhibition of p-Akt and p-mTOR, in vitro, decreased tumor cell VEGF-C and VEGF-D significantly. Therefore, we concluded that lymphangiogenesis of gastric cancer might be related to Akt/mTOR-VEGF-C/VEGF-D axis.

show abstract

Section: Discussionsupporting

confidence: 70%

Lymphangiogenesis in Gastric Cancer regulated through Akt/mTOR-VEGF-C/VEGF-D axis

et al. 2015

View full text Add to dashboard Cite

show abstract

“…The PI3K/Akt pathway is frequently activated in gastric carcinogenesis and vital to gastric cancer development [ 18 ]. This pathway was found to be activated by H. pylori infection both in vivo and in vitro , which is consistent with previous studies [ 17 , 19 – 22 ].…”

Section: Discussionmentioning

confidence: 99%

N‐Acetylcysteine Reduces ROS‐Mediated Oxidative DNA Damage and PI3K/Akt Pathway Activation Induced by Helicobacter pylori Infection

Xie

Lü

et al. 2018

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Background H. pylori infection induces reactive oxygen species- (ROS-) related DNA damage and activates the PI3K/Akt pathway in gastric epithelial cells. N-Acetylcysteine (NAC) is known as an inhibitor of ROS; the role of NAC in H. pylori-related diseases is unclear. Aim The aim of this study was to evaluate the role of ROS and the protective role of NAC in the pathogenesis of H. pylori-related diseases. Method An in vitro coculture system and an in vivo Balb/c mouse model of H. pylori-infected gastric epithelial cells were established. The effects of H. pylori infection on DNA damage and ROS were assessed by the comet assay and fluorescent dichlorofluorescein assay. The level of PI3K/Akt pathway-related proteins was evaluated by Western blotting. The protective role of N-acetylcysteine (NAC) was also evaluated with in vitro and in vivo H. pylori infection models. Results The results revealed that, in vitro and in vivo, H. pylori infection increased the ROS level and induced DNA damage in gastric epithelial cells. NAC treatment effectively reduced the ROS level and inhibited DNA damage in GES-1 cells and the gastric mucosa of Balb/c mice. H. pylori infection induced ROS-mediated PI3K/Akt pathway activation, and NAC treatment inhibited this effect. However, the gastric mucosa pathological score of the NAC-treated group was not significantly different from that of the untreated group. Furthermore, chronic H. pylori infection decreased APE-1 expression in the gastric mucosa of Balb/c mice. Conclusions An increased ROS level is a critical mechanism in H. pylori pathogenesis, and NAC may be beneficial for the treatment of H. pylori-related gastric diseases linked to oxidative DNA damage.

show abstract

“…The PI3K/Akt pathway is downstream of PTEN [ 14 ] and is frequently activated in gastric carcinogenesis and vital to gastric cancer development [ 41 ]. This pathway was found to be activated by H. pylori infection both in vivo and in vitro , which is consistent with previous studies [ 9 , 10 , 35 - 40 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

Phosphorylation and inactivation of PTEN at residues Ser380/Thr382/383 induced by Helicobacter pylori promotes gastric epithelial cell survival through PI3K/Akt pathway

Yang

Xie

et al. 2015

Oncotarget

View full text Add to dashboard Cite

Phosphorylation of PTEN at residues Ser380/Thr382/383 leads to loss of phosphatase activity and tumor suppressor function. Here, we found that phosphorylation of PTEN at residues Ser380/Thr382/383 was increased with gastric carcinogenesis, and more importantly, Helicobacter pylori was a trigger of this modification in chronic non-atrophic gastritis. H. pylori could phosphorylate and inactivate PTEN in vivo and in vitro, resulting in survival of gastric epithelial cells. Furthermore, stable expression of dominant-negative mutant PTEN or inhibition of Akt prevented the enhanced survival induced by H. pylori. These results indicate that PTEN phosphorylation at residues Ser380/Thr382/383 is a novel mechanism of PTEN inactivation in gastric carcinogenesis, and H. pylori triggers this modification, resulting in activation of the PI3K/Akt pathway and promotion of cell survival.

show abstract

Protein Kinase B Phosphorylation Correlates with Vascular Endothelial Growth Factor A and Microvessel Density in Gastric Adenocarcinoma

Cited by 9 publications

References 39 publications

Lymphangiogenesis in Gastric Cancer regulated through Akt/mTOR-VEGF-C/VEGF-D axis

Lymphangiogenesis in Gastric Cancer regulated through Akt/mTOR-VEGF-C/VEGF-D axis

N‐Acetylcysteine Reduces ROS‐Mediated Oxidative DNA Damage and PI3K/Akt Pathway Activation Induced by Helicobacter pylori Infection

Phosphorylation and inactivation of PTEN at residues Ser380/Thr382/383 induced by Helicobacter pylori promotes gastric epithelial cell survival through PI3K/Akt pathway

Contact Info

Product

Resources

About