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Endocrine Abstracts (2015) 37 EP165 | DOI: 10.1530/endoabs.37.EP165

1Department of Physiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 2College of Medicine, Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan.


Angiogenesis is a crucial physiological phenomenon in female reproductive cycle. Our previous studies have shown that progesterone could inhibit proliferation of human umbilical vein endothelial cells (HUVEC) through a p53-dependent mechanism, by which the levels of p21 and p27 protein were increased, subsequently inhibiting the CDK2 kinase activity, and finally impaired the transition of the cell from the G1 phase to the S phase. While previous studies had clearly demonstrated that p53 protein directly activates p21 expression though binding onto the p21 promoter, the p53-regulated p27 gene expression has not been reported. Accordingly, the aim of this research was to investigate the precise binding domains of p53 protein on the p27 promoter. Luciferase assay showed that the potential p53 binding region spans on sites 258–310 upstream the start codon of the p27 gene. Within this range, there are three potential binding fragments with 70% similarity of p53 consensus binding domain and between each fragment is separated by <13 bp. Deletion or TCCT sequence replacement at the internal site of anyone of these fragments resulted in an irresponsiveness to progesterone treatment, suggesting that all these three fragments are essential for p53 protein to regulate the p27 promoter activity. Moreover, immunoprecipitation and chromatin-immunoprecipitation analysis demonstrated that both the formation of p53-progesterone receptor complex in the nucleus and the binding of progesterone receptor onto the p53 binding fragment of the p27 promoter were increased by progesterone treatment, suggesting that progesterone receptor might be also involved in the p53-regulated the p27 promoter activity. To our knowledge, this is the first demonstration that progesterone up-regulated p27 expression in HUVEC through a p53-dependent pathway.

Disclosure: This work was supported by grant from NSC 100–2320-B-038-011 to Dr W-S Lee and grant from NSC 102-2320-B-038-023 and TMU101-AE1-B45 to Dr S-P Hsu.

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