期刊
FERTILITY AND STERILITY
卷 88, 期 2, 页码 326-332出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.fertnstert.2006.11.185
关键词
raloxifene; endothelium; proliferation; estrogen receptors; cell-cycle regulators; cyclin A; cyclin B 1
Objective: To examine the proliferative effect of of raloxifene on, human umbilical-vein endothelial cells (HUVECs), and to investigate whether there is an associated increased expression of some key regulators of the cell cycle. Design: Cell culture for different incubation times. Setting: University research laboratory. Patient(s): Sources of HUVECs. Intervention(s): Measurement of cell proliferation, of protein levels of cyclin A, cyclin B1, cyclin D1, cyclin-dependent protein kinase (CDK) 2, CDK4, and p27(Kip1), and of messenger RNA expression of cyclin A, cyclin B1, and p27(Kip1) Main Outcome Measure(s): Cell proliferation was measured by the 3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, the bromo-2'-deoxyuridine assay, and the sodium 3'-[1-(phenylaminocarbonyl)-3,4-tetrazolium]-bis (4-methoxy-6-nitro) benzene sulfonic acid hydrate assay. Changes in protein expression were measured by immunoblotting, and modifications in gene expression were measured by quantitative real-time polymerase chain reaction. Result(s): Both 1 nM and 10 nM of either E-2 or raloxifene achieved a similar increase in cell proliferation. The pure antiestrogen ICI 182780 only blocked the E-2-induced proliferative effect. Western blot experiments detected an increase in the expression of only cyclin A and B1, and a decreasing trend for p27(Kip1). Enhancements in gene expression were observed in response to E-2 and raloxifene for cyclin A and B1. No significant changes were found for P27(Kip1). The ICI 182780 effectively abrogated the increased gene expression associated with E-2 for cyclin B1, but not for cyclin A. In contrast, ICI 182780 was ineffective in the case of raloxifene. Conclusion(s): Raloxifene increased the proliferation of HUVECs in association with enhanced gene expression of cyclins A and B1.
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