Lymphatic endothelial reprogramming of vascular endothelial cells by the Prox‐1 homeobox transcription factor
Identifieur interne : 009675 ( Main/Exploration ); précédent : 009674; suivant : 009676Lymphatic endothelial reprogramming of vascular endothelial cells by the Prox‐1 homeobox transcription factor
Auteurs : Tatiana V. Petrova [États-Unis] ; Taija M Kinen [États-Unis] ; Tomi P. M Kel [États-Unis] ; Janna Saarela [États-Unis] ; Ismo Virtanen [États-Unis] ; Robert E. Ferrell [États-Unis] ; David N. Finegold [États-Unis] ; Dontscho Kerjaschki [Autriche] ; Seppo Yl Erttuala [Finlande] ; Kari Alitalo [États-Unis, Finlande]Source :
- The EMBO Journal [ 0261-4189 ] ; 2002-09-02.
Abstract
Lymphatic vessels are essential for fluid homeostasis, immune surveillance and fat adsorption, and also serve as a major route for tumor metastasis in many types of cancer. We found that isolated human primary lymphatic and blood vascular endothelial cells (LECs and BECs, respectively) show interesting differences in gene expression relevant for their distinct functions in vivo. Although these phenotypes are stable in vitro and in vivo, overexpression of the homeobox transcription factor Prox‐1 in the BECs was capable of inducing LEC‐specific gene transcription in the BECs, and, surprisingly, Prox‐1 suppressed the expression of ∼40% of the BEC‐specific genes. Prox‐1 did not have global effects on the expression of LEC‐specific genes in other cell types, except that it up‐regulated cyclin E1 and E2 mRNAs and activated the cyclin e promoter in various cell types. These data suggest that Prox‐1 acts as a cell proliferation inducer and a fate determination factor for the LECs. Furthermore, the data provide insights into the phenotypic diversity of endothelial cells and into the possibility of transcriptional reprogramming of differentiated endothelial cells.
Url:
- https://api.istex.fr/document/40A29E8710124BFC26B3BB6B998B5DF45CDE55B9/fulltext/pdf
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC125413
DOI: 10.1093/emboj/cdf470
Affiliations:
- Autriche, Finlande, États-Unis
- Pennsylvanie, Uusimaa, Vienne (Autriche)
- Helsinki, Pittsburgh, Vienne (Autriche)
- Université d'Helsinki, Université de Pittsburgh
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Le document en format XML
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<front><div type="abstract">Lymphatic vessels are essential for fluid homeostasis, immune surveillance and fat adsorption, and also serve as a major route for tumor metastasis in many types of cancer. We found that isolated human primary lymphatic and blood vascular endothelial cells (LECs and BECs, respectively) show interesting differences in gene expression relevant for their distinct functions in vivo. Although these phenotypes are stable in vitro and in vivo, overexpression of the homeobox transcription factor Prox‐1 in the BECs was capable of inducing LEC‐specific gene transcription in the BECs, and, surprisingly, Prox‐1 suppressed the expression of ∼40% of the BEC‐specific genes. Prox‐1 did not have global effects on the expression of LEC‐specific genes in other cell types, except that it up‐regulated cyclin E1 and E2 mRNAs and activated the cyclin e promoter in various cell types. These data suggest that Prox‐1 acts as a cell proliferation inducer and a fate determination factor for the LECs. Furthermore, the data provide insights into the phenotypic diversity of endothelial cells and into the possibility of transcriptional reprogramming of differentiated endothelial cells.</div>
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