Microarray analysis on the role of VEGF signaling pathway for the growth and metastasis of murine bladder carcinoma
- Author:
Feng WANG
1
Author Information
1. Central Experimental Laboratory
- Publication Type:Journal Article
- Keywords:
Bladder neoplasms, experimental;
Gene expression profiling;
Vascular endothelial growth factor
- From:
Tumor
2007;27(11):847-852
- CountryChina
- Language:Chinese
-
Abstract:
Objective: Angiogenesis has been indicated to play pivotal roles in both the initial development and metastasis of solid tumor. Among the numerous factors, vascular endothelial growth factor (VEGF) is widely recognized. This study aimed to discuss the role of VEGF in angiogenesis and its relationship with the growth and metastasis of murine bladder carcinoma as well as the action mechanism. Methods: The BTT-VEGFanti cells, which constitutively express the anti-sense VEGF121 gene, were derived by stably transfecting the BTT-T739 cells with the anti-sense VEGF121 plasmid. The effects of VEGF on the growth rates, tumor formation capability, proliferation and metastasis of the two cells both in vitro and in vivo were observed. Isolated and purified mRNA from the two kinds of cells and tissues were reverse transcribed and hybridized with cDNA gene chips including 16,361 human genes. The differentiated gene expression was recorded and the changes in the gene expression profiles were analyzed. Real-time RT-PCR was used to identify the microarray results. Some genes with more than 2 fold changes were searched in iPath for discovering the related pathways. Results: Anti-sense VEGF expression plasmid selectively inhibited the production of VEGF by tumor cells. The declined level of VEGF had no effects on the growth rate and growth pattern of tumor cells in vitro. But the tumor growth was significantly slowed and metastasis was significantly inhibited in vivo after treatment with anti-sense VEGF expression plasmid. Microarray hybridization results showed that there existed 82 common genes with more than 2 fold differentiated expression in tumor cells and tumor tissues with high or low expression of VEGF. Twenty-three genes (signaling density ≥40) were further selected. Out of the 23 genes, 17 genes were found to be homo geneous by comparison with murine cDNA and EST database according to the probe sequence in cDNA microarray. The functions of 9 genes were already known. They were not known genes in induction of angiogenesis indicating that several novel genes participated in the tumor angiogenesis. Conclusion: VEGF may influence the growth rate and metastasis of murine bladder carcinoma by regulating tumor angiogenesis. VEGF exertes its effects through a complex network involving multiple genes and signaling pathways.
