» Articles » PMID: 11819817

Expression of Vascular Endothelial Growth Factor and Its Role in Oncogenesis of Human Gastric Carcinoma

Overview
Specialty Gastroenterology
Date 2002 Jan 31
PMID 11819817
Citations 30
Authors
Affiliations
Soon will be listed here.
Abstract

Aim: To establish the role of vascular endothelial growth factor (VEGF) in the oncogenesis of human gastric carcinoma more directly.

Methods: The expression of VEGF and its receptor kinase-domain insert containing receptor (KDR) in human gastric cancer tissue were observed by immunohistochemical staining. VEGF levels were manipulated in human gastric cancer cell using eukaryotic expression constructs designed to express the complete VEGF(165) complimentary DNA in either the sense or antisense orientation. The biological changes of the cells were observed in which VEGF was up-regulated or down-regulated.

Results: VEGF-positive rate was 50%, and VEGF was mainly localized in the cytoplasm and membrane of the tumor cells, while KDR was mainly located in the membrane of vascular endothelial cells in gastric cancer tissues and peri-cancerous tissue. In 2 cases of 50 specimens, the gastric cancer cells expressed KDR, localized in both the cytoplasm and membrane. Introduction of VEGF(165) antisense into human gastric cancer cells (SGC-7901, immunofluorescence intensity, 31.6%)) resulted in a significant reduction in VEGF-specific messenger RNA and total and cell surface VEGF protein (immunofluorescence intensity, 8.9%) (P<0.05). Conversely, stable integration of VEGF(165) in the sense orientation resulted in an increase in cellular and cell surface VEGF (immunofluorescence intensity, 75.4%) (P<0.05). Lowered VEGF levels were associated with a marked decrease in the growth of nude mouse xenografted tumor (at 33 days postimplantation, tumor volume: 345.40 +/- 136.31 mm3)(P<0.05 vs control SGC-7901 group: 1534.40 +/- 362.88 mm3), whereas up-regulation of VEGF resulted in increased xenografted tumor size (at 33 days postimplantation, tumor volume: 2350.50 +/- 637.70 mm3) (P<0.05 vs control SGC-7901 group).

Conclusion: This study provides direct evidence that VEGF plays an important role in the oncogenesis of human gastric cancer.

Citing Articles

Calreticulin regulates vascular endothelial growth factor-A mRNA stability in gastric cancer cells.

Lee P, Chiang J, Chen C, Chien Y, Chen W, Huang C PLoS One. 2019; 14(11):e0225107.

PMID: 31725767 PMC: 6855450. DOI: 10.1371/journal.pone.0225107.


The VEGF -634G>C promoter polymorphism is associated with risk of gastric cancer.

Guan X, Zhao H, Niu J, Tang D, Ajani J, Wei Q BMC Gastroenterol. 2009; 9:77.

PMID: 19835575 PMC: 2771032. DOI: 10.1186/1471-230X-9-77.


Polymorphisms of TGFB1 and VEGF genes and survival of patients with gastric cancer.

Guan X, Zhao H, Niu J, Tan D, Ajani J, Wei Q J Exp Clin Cancer Res. 2009; 28:94.

PMID: 19566948 PMC: 2717936. DOI: 10.1186/1756-9966-28-94.


Histopathological predictor for regional lymph node metastasis in gastric cancer.

Morita H, Ishikawa Y, Akishima-Fukasawa Y, Ito K, Akasaka Y, Nishimura C Virchows Arch. 2008; 454(2):143-51.

PMID: 19104832 DOI: 10.1007/s00428-008-0717-3.


Significance of vascular endothelial growth factor expression and its correlation with inducible nitric oxide synthase in gastric cancer.

Song Z, Wen S, Peng J, Huang X, Qian K World J Gastroenterol. 2004; 10(9):1250-5.

PMID: 15112337 PMC: 4622761. DOI: 10.3748/wjg.v10.i9.1250.


References
1.
Kolch W, Heidecker G, Troppmair J, Yanagihara K, Bassin R, Rapp U . Raf revertant cells resist transformation by non-nuclear oncogenes and are deficient in the induction of early response genes by TPA and serum. Oncogene. 1993; 8(2):361-70. View

2.
Tsuzuki Y, Fukumura D, Oosthuyse B, Koike C, Carmeliet P, Jain R . Vascular endothelial growth factor (VEGF) modulation by targeting hypoxia-inducible factor-1alpha--> hypoxia response element--> VEGF cascade differentially regulates vascular response and growth rate in tumors. Cancer Res. 2000; 60(22):6248-52. View

3.
Saleh M, Stacker S, Wilks A . Inhibition of growth of C6 glioma cells in vivo by expression of antisense vascular endothelial growth factor sequence. Cancer Res. 1996; 56(2):393-401. View

4.
Xu C, Pan B . Current status of gene therapy in gastroenterology. World J Gastroenterol. 2002; 4(1):85-89. PMC: 4767776. DOI: 10.3748/wjg.v4.i1.85. View

5.
Inoue K, Ozeki Y, Suganuma T, Sugiura Y, Tanaka S . Vascular endothelial growth factor expression in primary esophageal squamous cell carcinoma. Association with angiogenesis and tumor progression. Cancer. 1997; 79(2):206-13. DOI: 10.1002/(sici)1097-0142(19970115)79:2<206::aid-cncr2>3.0.co;2-i. View