Inhibition of Adenovirus-mediated Human Mage-d1 on Angiogenesis in Vitro and in Vivo.
From: Medical College of Yangzhou University, 16 Huai Hai Road, Yangzhou 225000, Jiangsu Province, PR China. weiganshen@yahoo.com.cn
Molecular and cellular biochemistry
- Publish Date: Jun 2007
- ISSN: 0300-8177
- Volume: 300
- Issue: 1-2
- Pages: 89-99
- Medium: Print
- Language: English
- Citation (JAMA): Shen Wei-Gan, Xue Qing-Yu, Zhu Jun, et al. Inhibition of Adenovirus-mediated Human Mage-d1 on Angiogenesis in Vitro and in Vivo.. Mol. Cell. Biochem. Jun 2007;300:89-99
Abstract
MAGE-D1 is a member of the MAGE family of proteins, and functions as an adaptor that mediates multiple signaling pathways. The current study for the first time provides evidence for a role of MAGE-D1 in the negative regulation of angiogenic activity in vitro and in vivo models. Our findings showed that MAGE-D1 over-expression significantly suppressed the angiogenic key events such as endothelial cell migration and invasion, adhesion on collagen I substrate, and in vitro differentiation into tube-like structures under both normoxic and hypoxic conditions. MAGE-D1 over-expression also inhibited in vivo angiogenesis in Matrigel plugs that were implanted subcutaneously in mice. With further experiments, we revealed that MAGE-D1 over-expression disrupted actin cytoskeleton organization and lamellipodia formation, and down-regulated HIF-1-dependent gene expression in endothelial cells under hypoxic conditions. These findings demonstrate a new function of MAGE-D1 in the regulation of angiogenesis and provide new insight into the ability of MAGE-D1 to suppress the growth and angiogenic response of endothelial cells by interfering with HIF-1-dependent gene expression, and actin cytoskeleton reorganization, suggesting that MAGE-D1 might be a novel inhibitor of angiogenesis in vitro and in vivo.
Mesh Headings (Keywords): Actins, Adenoviridae, Antigens, Neoplasm, Cell Adhesion, Cell Movement, Cells, Cultured, Collagen, Cytoskeleton, Drug Combinations, Endothelial Cells, Gene Expression Regulation, Genes, Reporter, Humans, Hypoxia-Inducible Factor 1, Laminin, Neoplasm Proteins, Neovascularization, Physiologic, Proteoglycans, Pseudopodia
Check for Full Text / PubMed Unique Identifier (PMID): 17149546
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