title: Endocan is a VEGF-A and PI3K regulated gene with increased expression in human renal cancer.
abstract: 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.
authors.affiliation: Department of Genetics and Pathology, the Rudbeck Laboratory, Uppsala University, S-751 85 Uppsala, Sweden.
authors.forename: Emma
authors.initials: E
authors.lastname: Rennel
authors.forename: Sofie
authors.initials: S
authors.lastname: Mellberg
authors.forename: Anna
authors.initials: A
authors.lastname: Dimberg
authors.forename: Ludvig
authors.initials: L
authors.lastname: Petersson
authors.forename: Johan
authors.initials: J
authors.lastname: Botling
authors.forename: Adam
authors.initials: A
authors.lastname: Ameur
authors.forename: Jakub Orzechowski
authors.initials: JO
authors.lastname: Westholm
authors.forename: Jan
authors.initials: J
authors.lastname: Komorowski
authors.forename: Philippe
authors.initials: P
authors.lastname: Lassalle
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Cross
authors.forename: Pär
authors.initials: P
authors.lastname: Gerwins
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism* / Q000494:pharmacology; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism* / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011509:Proteoglycans / Q000378:metabolism* / Q000494:pharmacology; D014158:Transcription, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D009363:Neoplasm Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011509:Proteoglycans; D042461:Vascular Endothelial Growth Factor A; C101134:ESM1 protein, human; C467484:VEGFA protein, human