title: 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.
authors.affiliation: Department of Cellular Responses and Dynamics, CEA-INSERM-Joseph Fourier University EMI 0219, CEA-Grenoble, France.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Prandini
authors.forename: Inge
authors.initials: I
authors.lastname: Dreher
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bouillot
authors.forename: Souhila
authors.initials: S
authors.lastname: Benkerri
authors.forename: Thomas
authors.initials: T
authors.lastname: Moll
authors.forename: Philippe
authors.initials: P
authors.lastname: Huber
mesh_terms: D000818:Animals; D015703:Antigens, CD; D001483:Base Sequence; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D000099152:Cadherin 5
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