Markers CD40, VEGF, AKT, PI3K, and S100 Correlate with Tumor Stage in Gastric Cancer

Tian, Wenyan; Chen, Weichang; Li, Rui; Liu, Lei

doi:10.1159/000346675

Cited by 14 publications

(13 citation statements)

References 23 publications

(30 reference statements)

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“…We confirmed its elevated expression by using IHC for detection of VEGF in gastric cancer tissues. Dysregulation of VEGF was reported to be through the PI3K‐Akt pathway in tumors [Ma et al, ; Shafee et al, ; Liu et al, ; Tian et al, ]. We observed that enforced BMP9 expression resulted in reduced expression of VEGF gene and protein in gastric cancer cells both in vitro and in vivo, and inhibition of the PI3K‐Akt pathway with LY294002 potentiated BMP9‐induced VEGF suppression.…”

Section: Discussionmentioning

confidence: 54%

Inactivation of the Phosphatidylinositol 3‐Kinase/Akt Pathway is Involved in BMP9‐mediated Tumor‐suppressive Effects in Gastric Cancer Cells

Duan

et al. 2015

J of Cellular Biochemistry

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Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily signaling factors. Expression of several BMPs (BMP2, BMP4, and BMP7) is correlated to poor prognosis in gastric cancer patients. The function of BMP9, the latest discovered and most powerful osteogenetic factor, in gastric cancer is relatively unclear. In this report, we investigated the expression, function and underlying molecular mechanisms of BMP9 in gastric cancer. The results show that BMP9 expression was markedly decreased in gastric cancer tissues and cell lines. Enforced BMP9 expression in the gastric cancer cell lines SGC-7901 and MNK-45 increased apoptosis and reduced viability and migration. The in vivo function of BMP9 was evaluated in a xenograft mouse model. Tumors derived from SGC-7901 cells with enforced BMP9 expression (SGC-7901/BMP9) showed significantly reduced size and weight compared to that from control cells. Enforced BMP9 expression resulted in decreased Akt activity shown as lower levels of phosphorylation at Ser473 and Thr308 in Akt. The PI3K/Akt inhibitor LY294002 potentiated BMP9's viability and migration suppression, and apoptosis induction, which was associated with reduced expression of snail and VEGF and increased expression of E-cadherin. In addition, tumors derived from SGC-7901/BMP9 showed reduced Akt activity and VEGF expression, and increased E-cadherin expression. Therefore, our studies reveal for the first time that inhibition of the PI3K-Akt pathway is involved in the tumor suppressor effects of BMP9 in gastric cancer.

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Section: Discussionmentioning

confidence: 54%

Inactivation of the Phosphatidylinositol 3‐Kinase/Akt Pathway is Involved in BMP9‐mediated Tumor‐suppressive Effects in Gastric Cancer Cells

Duan

et al. 2015

J of Cellular Biochemistry

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“…Patients testing positive for the abnormal expression of the PI3K/AKT/mTOR pathway were more likely to be in the late stages of gastric cancer with a lower survival rate. [4][5][6][7] Several drugs targeting PI3K/AKT/mTOR pathways are currently in clinical trials for gastric cancer, including PI3K inhibitor (LY294002, MK2206), AKT inhibitor (MLN1117), and mTOR inhibitor (everolimus). [8][9][10][11] PI3K inhibitor and AKT inhibitor monotherapy showed promising effects in Phases I-II, while mTOR inhibitor failed to improve survival in the GRANITE-1 Stage III trial for advanced gastric cancer.…”

mentioning

confidence: 99%

“…A score 4 was considered to be positive. 4,5,7 statistical analysis Statistical Package for the Social Sciences (SPSS) version 16.0 (SPSS Inc., Chicago, IL, USA) was used for the statistical analysis. The correlation between PI3K, p-AKT, and p-mTOR expression and patient clinicopathologic factors was analyzed using the χ 2 test.…”

mentioning

confidence: 99%

2381 The expression of the PI3K/AKT/mTOR pathway in gastric cancer and its role in gastric cancer prognosis

Ying¹,

He²,

Sun³

et al. 2015

European Journal of Cancer

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“…Another study also showed increased VEGF expression level in the advanced stages of GC compared to that in the earlier stages. 34 …”

Section: Discussionmentioning

confidence: 99%

Expression Levels of Vascular Endothelial Growth Factors A and C in Patients with Peptic Ulcers and Gastric Cancer

et al. 2014

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PurposeVascular endothelial growth factor (VEGF) is one of the most important growth factors for metastatic tumors. To clarify the role of VEGF-A and C in patients with peptic ulcer disease (PUD) or gastric cancer (GC), we evaluated the expression levels of these two molecules. We also analyzed the effect of Helicobacter pylori infection on VEGF-A and C expression levels.Materials and MethodsPatients with dyspepsia who needed diagnostic endoscopy were selected and divided into three groups: non-ulcer dyspepsia (NUD), PUD, and GC, according to their endoscopic and histopathological results. Fifty-two patients with NUD, 50 with PUD, and 38 with GC were enrolled in this study. H. pylori infection was diagnosed by the rapid urease test. After RNA extraction and synthesis of cDNA, the expression levels of VEGF-A and C were determined by quantitative reverse transcriptase polymerase chain reaction.ResultsThe VEGF-C expression level in the PUD and GC groups was significantly higher than that in the NUD group. Moreover, the VEGF-A expression level in the PUD and GC groups was higher than in the NUD group, although the differences were not statistically significant. Significant positive correlations were also observed between the expression levels of these two molecules in the PUD and GC groups. In addition, the expression levels of these two molecules were higher in H. pylori positive patients with PUD or GC than in H. pylori negative patients of the same groups; however, these differences did not reach statistical significance.ConclusionsUp-regulation of VEGF-C expression during gastric mucosal inflammation may play a role in the development of peptic ulcers or GC.

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Markers CD40, VEGF, AKT, PI3K, and S100 Correlate with Tumor Stage in Gastric Cancer

Cited by 14 publications

References 23 publications

Inactivation of the Phosphatidylinositol 3‐Kinase/Akt Pathway is Involved in BMP9‐mediated Tumor‐suppressive Effects in Gastric Cancer Cells

Inactivation of the Phosphatidylinositol 3‐Kinase/Akt Pathway is Involved in BMP9‐mediated Tumor‐suppressive Effects in Gastric Cancer Cells

2381 The expression of the PI3K/AKT/mTOR pathway in gastric cancer and its role in gastric cancer prognosis

Expression Levels of Vascular Endothelial Growth Factors A and C in Patients with Peptic Ulcers and Gastric Cancer

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