401. Identification of derlin-1 as a novel growth factor-responsive endothelial antigen by suppression subtractive hybridization.
- Author
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Ran Y, Jiang Y, Zhong X, Zhou Z, Liu H, Hu H, Lou JN, and Yang Z
- Subjects
- Antigens, Neoplasm genetics, Antigens, Neoplasm metabolism, Apoptosis, Carcinoma, Hepatocellular blood supply, Carcinoma, Hepatocellular metabolism, Carcinoma, Hepatocellular pathology, Cell Proliferation, Cell Survival, Endothelium, Vascular cytology, Humans, Liver Neoplasms blood supply, Liver Neoplasms metabolism, Liver Neoplasms pathology, Membrane Proteins antagonists & inhibitors, Membrane Proteins genetics, Nucleic Acid Hybridization methods, Up-Regulation, Vascular Endothelial Growth Factor A pharmacology, Endothelium, Vascular metabolism, Membrane Proteins metabolism, Neoplasms blood supply, Neovascularization, Pathologic
- Abstract
Endothelial cells play an important regulatory role in embryonic development, reproductive functions, tumor growth and progression. In the present study, the suppression subtractive hybridization (SSH) method was employed to identify differentially expressed genes between non-stimulated endothelial cells and activated endothelial cells. Following mRNA isolation of non-stimulated and hepatocellular carcinoma homogenate-stimulated cells, cDNAs of both populations were prepared and subtracted by suppressive PCR. Sequencing of the enriched cDNAs identified a couple of genes differentially expressed, including derlin-1. Derlin-1 was significantly up-regulated by tumor homogenates, VEGF, and endothelial growth supplements in a dose-dependent manner. Knock-down of derlin-1 triggered endothelial cell apoptosis, inhibited endothelial cell proliferation, and blocked the formation of a network of tubular-like structures. Our data reveal that derlin-1 is a novel growth factor-responsive endothelial antigen that promotes endothelial cell survival and growth.
- Published
- 2006
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