The human VE-cadherin promoter is subjected to organ-specific regulation and is activated in tumour angiogenesis.

Abstract:

:Vascular endothelial (VE)-cadherin is exclusively expressed at interendothelial junctions of normal and tumour vessels. In this report, we characterized the transcriptional activity of the human VE-cadherin promoter. Transient transfection assays revealed that sequences at positions --1135/-744 and -166/-5 base pairs are critical for promoter activity in endothelial cells. We show that specific sequences in the proximal region interact with Ets and Sp1 family members. Transgenic mice were created and the human VE-cadherin promoter was able to confer correct temporal and spatial expression on the LacZ gene in embryos. In adults, the transgene was specifically and strongly expressed in the lung, heart, ovary, spleen and kidney glomeruli, whereas expression was weak or absent in the vasculature of other organs, including the brain, thymus, liver and skeletal muscle. Neovessels in tumour grafts and Matrigel implants harboured strong stainings, indicating that promoter activity is enhanced in angiogenic situations. Furthermore, Matrigel and transfection assays showed that VE-cadherin promoter is subjected to bFGF induction. Transgene expression was also noticed in extravascular sites of the central nervous system, suggesting that silencer elements may be located elsewhere in the gene. These results are a first step towards addressing the organ- and tumour-specific regulation of the VE-cadherin gene.

journal_name

Oncogene

journal_title

Oncogene

authors

Prandini MH,Dreher I,Bouillot S,Benkerri S,Moll T,Huber P

doi

10.1038/sj.onc.1208483

subject

Has Abstract

pub_date

2005-04-21 00:00:00

pages

2992-3001

issue

18

eissn

0950-9232

issn

1476-5594

pii

1208483

journal_volume

24

pub_type

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