Progesterone inhibits human endothelial cell proliferation through a p53-dependent pathway |
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Authors: | S-P Hsu P-Y Ho S-H Juan Y-C Liang W-S Lee |
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Institution: | (1) Medical College of Yangzhou University, 16 Huai Hai Road, Yangzhou, 225000, Jiangsu Province, PR China;(2) Yangzhou Educational College, Yangzhou, PR China |
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Abstract: | Previous studies have shown that progesterone inhibits endothelial cell proliferation through a nuclear receptor-mediated
mechanism. Here, we further demonstrate that progesterone at physiologic levels (5 – 500 nM) dose- and time-dependently inhibited
DNA synthesis of cultured human umbilical vein endothelial cells (HUVEC). The mRNA and protein levels of p21, p27, and p53
in HUVEC were increased by progesterone. The formation of CDK2-p21 and CDK2-p27 were increased and the CDK2 activity was decreased
in the progesterone-treated HUVEC. The progesterone-inhibited 3H]thymidine incorporation was completely blocked when the
expressions of p21 and p27 were knocked-down together. Transfection of HUVEC with dominant negative p53 cDNA prevented the
progesterone-induced increases in p21 and p27 promoter activity and protein level, decreases in thymidine incorporation, and
capillary-like tube formation. Matrigel angiogenesis assay in mice demonstrated the antiangiogenic effect of progesterone
in vivo. These findings demonstrate for the first time that progesterone inhibited endothelial cell proliferation through a p53-dependent
pathway.
Received 28 July 2008; received after revision 25 September 2008; accepted 26 September 2008 |
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Keywords: | " target="_blank"> Progesterone angiogenesis p53 p27 p21 |
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