ABSTRACT

Fibroblast growth factor-2 (FGF2) is a potent angiogenic factor that 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, we have identified the stress-inducible genes A170, GADD45, and GADD153 as upregulated after endothelial cell activation by FGF2 transduction. Also, their expression was rapidly induced in parental MAE cells by treatment with recombinant FGF2. 

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.

 Oncogene (2002) 21:2433-2440