Dell'Era Patrizia, Coco Laura, Ronca Roberto, Sennino Barbara, Presta Marco
Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brescia, 25123 Brescia, Italy.
Oncogene. 2002 Apr 4;21(15):2433-40. doi: 10.1038/sj.onc.1205301.
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.
成纤维细胞生长因子-2（FGF2）对内皮细胞发挥旁分泌和自分泌功能。过表达FGF2的小鼠主动脉内皮细胞（FGF2-T-MAE细胞）接种于免疫缺陷小鼠时会诱发机会性血管内皮瘤样肿瘤。为了评估FGF2介导的激活对转化内皮细胞基因表达谱的影响，我们对FGF2-T-MAE细胞和亲本MAE细胞进行了消减抑制杂交分析。还通过用32P标记的cDNA进行基因宏阵列杂交，比较了这两种细胞群体的差异基因表达。这两种方法鉴定出了27种转录本，其在内皮细胞中的表达被FGF2上调。除了一个未知基因外，差异表达的转录本编码参与细胞周期调节、分化和细胞黏附的蛋白质。其中，应激诱导基因A170、GADD45和GADD153通过FGF2转染或重组生长因子处理而上调。在裸鼠中由亲本或FGF2转染的MAE细胞产生的血管肿瘤中也诱导了它们的表达。本研究扩展了参与肿瘤血管生成和/或内皮细胞转化的基因数量，这一发现可能对发现血管生成抑制治疗的新靶点具有启示意义。
