title: Gene expression profile in fibroblast growth factor 2-transformed endothelial cells.
abstract: Fibroblast growth factor-2 (FGF2) exerts paracrine and autocrine functions on endothelial cells. FGF2-overexpressing murine aortic endothelial cells (FGF2-T-MAE cells) induce opportunistic hemangioendothelioma-like tumors when inoculated in immunodeficient mice. To evaluate the impact of FGF2-mediated activation on gene expression profile in transformed endothelial cells, we performed subtractive suppression hybridization analysis between FGF2-T-MAE cells and parental MAE cells. The two cell populations were compared for differential gene expression also by gene macroarray hybridization with 32P-labeled cDNAs. The two approaches allowed the identification of 27 transcripts whose expression was upregulated by FGF2 in endothelial cells. With the exception of one unknown gene, the differentially expressed transcripts encoded for proteins involved in the modulation of cell cycle, differentiation, and cell adhesion. Among them, the stress-inducible genes A170, GADD45 and GADD153 are upregulated by FGF2 transfection or recombinant growth factor treatment. Their expression was also induced in vascular tumors originated by parental or FGF2-transfected MAE cells in nude mice. This study extends the number of genes involved in tumor angiogenesis and/or endothelial cell transformation, a finding with possible implications for the discovery of novel targets for angiostatic therapy.
authors.affiliation: Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brescia, 25123 Brescia, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Dell'Era
authors.forename: Laura
authors.initials: L
authors.lastname: Coco
authors.forename: Roberto
authors.initials: R
authors.lastname: Ronca
authors.forename: Barbara
authors.initials: B
authors.lastname: Sennino
authors.forename: Marco
authors.initials: M
authors.lastname: Presta
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D004730:Endothelium, Vascular / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000502:physiology*; D020869:Gene Expression Profiling; D051379:Mice; D008819:Mice, Nude; D009383:Neoplasms, Vascular Tissue / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
chemical_list: D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2