Endocan is a VEGF-A and PI3K regulated gene with increased expression in human renal cancer
An in vitro model of VEGF-A-induced angiogenesis was used to generate transcription profiles of human microvascular endothelial cells. Microarray analysis showed increased transcription of genes known to regulate angiogenesis, but also genes that previously have not been firmly associated with angio...
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Veröffentlicht in: | Experimental cell research 2007-04, Vol.313 (7), p.1285-1294 |
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Sprache: | eng |
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Zusammenfassung: | An
in vitro model of VEGF-A-induced angiogenesis was used to generate transcription profiles of human microvascular endothelial cells. Microarray analysis showed increased transcription of genes known to regulate angiogenesis, but also genes that previously have not been firmly associated with angiogenesis such as
endocan,
pinin,
plakophilin,
phosphodiesterase 4B and
gelsolin. Increased
endocan mRNA levels in response to VEGF-A in endothelial cells and in human renal cancer have previously been reported. We now show increased endocan protein levels in VEGF-A treated endothelial cells and in human renal clear cell carcinoma. Increased protein expression was observed both in tumor cells and in a subset of tumor vessels, while expression in normal kidney tissue was low. VEGF-A seemed to be a specific inducer of
endocan transcription since FGF-2, PDGF-BB, HGF/SF and EGF did not alter expression levels. Inhibition of PI3K with LY294002 caused a 12-fold increase in
endocan transcription suggesting a repressive function of PI3K. In contrast inhibition of Src or MEK, which are signaling pathways activated by VEGF-A, did not influence basal or VEGF-A-induced
endocan levels. In conclusion our study shows that, among angiogenic growth factors, VEGF-A is a specific inducer of
endocan transcription which is translated into increased protein levels in VEGF-A treated endothelial cells. Increased endocan protein expression in human renal cancer suggests a role in tumor growth. |
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ISSN: | 0014-4827 1090-2422 1090-2422 |
DOI: | 10.1016/j.yexcr.2007.01.021 |