Overexpression of caveolin-1 inhibits endothelial cell proliferation by arresting the cell cycle at G0/G1 phase
| Autor: | Andrew R. Beardsley, Kai Fang, Jun Liu, Wei Fu, Xinghui Sun, Michael P. Lisanti |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Angiogenesis
Caveolin 1 Cell Cycle G1 Phase Endothelial Cells Cell Biology Cell cycle Biology Resting Phase Cell Cycle Growth Inhibitors Cell biology Endothelial stem cell Vascular endothelial growth factor B Vascular endothelial growth factor A Gene Expression Regulation Mitogen-activated protein kinase Caveolae biology.protein Humans Molecular Biology Cells Cultured Developmental Biology Cell Proliferation |
| Zdroj: | Cell cycle (Georgetown, Tex.). 6(2) |
| ISSN: | 1551-4005 |
| Popis: | Angiogenesis, the development of new blood vessels from preexisting capillary, is required for tumor growth and metastasis. The process is not fully understood yet, but involves endothelial cell proliferation, migration and differentiation. Recently, we have shown that overexpression of caveolin-1, a putative transformation suppressor gene, inhibits VEGFR-2 and MEK-1-mediated mitogenic signal to the nucleus. Conversely, angiogenic activators suppress caveolin-1 expression in endothelial cells. However, whether caveolin-1 expression affects endothelial cell proliferation is not clear. In the present study, we infect human endothelial cells with adenovirus expressing caveolin-1 and show that transient overexpression of caveolin-1 dramatically inhibits the proliferation of human endothelial cells. Consistent with caveolin-1 functioning as an inhibitor for protein kinases, overexpression of caveolin-1 inhibits the activity of VEGFR-2 (KDR) and down-stream p42/44 MAP kinase. Furthermore, overexpression of caveolin-1 prevents VEGF-induced down-regulation of the cyclin-dependent kinase inhibitor p27(kip1) and Rb phosphorylation, and subsequently arrests endothelial cells in the G(0)/G(1) phase. Thus, our results suggest that caveolin-1, as a negative regulator of endothelial cell proliferation, may be a potential target for the control of angiogenesis. |
| Databáze: | OpenAIRE |
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