title: Overexpression of caveolin-1 inhibits endothelial cell proliferation by arresting the cell cycle at G0/G1 phase.
abstract: 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.
authors.affiliation: Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia 26506-9229, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Fang
authors.forename: Wei
authors.initials: W
authors.lastname: Fu
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Beardsley
authors.forename: Xinghui
authors.initials: X
authors.lastname: Sun
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lisanti
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
mesh_terms: D051242:Caveolin 1 / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D016193:G1 Phase / Q000235:genetics* / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D006131:Growth Inhibitors / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D006801:Humans; D016192:Resting Phase, Cell Cycle / Q000235:genetics* / Q000502:physiology
chemical_list: D051242:Caveolin 1; D006131:Growth Inhibitors