Indispensable role of the transcription factor PEBP2/CBF in angiogenic activity of a murine endothelial cell MSS31
Indispensable role of the transcription factor PEBP2/CBF in angiogenic activity of a murine endothelial cell MSS31
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DOI：
10.1038/sj.onc.1203257
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发表时间：
2000-01-06
期刊：
影响因子：
8
通讯作者：
Sato, Y
中科院分区：
文献类型：
--
作者：
Namba, K;Abe, M;Sato, Y
缺乏AML 1/PEBP 2 α B/CBFa 2基因或PEBP 2 β/CBF B基因的小鼠表现出永久性造血缺陷，并由于中枢神经系统出血而在子宫内死亡。胚胎中的造血被认为与血管发育密切相关，在此我们检测了PEBP 2/CBF除了在永久性造血中起作用之外是否在血管生成中起任何作用。我们发现AML 1/PEBP 2 α B/CBFa 2、PEBP 2 α A/CBFa 1和PEBP 2 β/CBF B b在小鼠内皮细胞系MISS 31中表达，这些分子作为细胞的表达，因为PEBP 2/CBF的DNA结合活性被血管生成生长因子如bFGF和VEGF增强。为了进一步阐明PEBP 2/CF在血管生成中的作用，我们建立了PEBP 2 β-MYH 11基因的永久转染子，该基因与α亚基的runt结构域相互作用并以显性干扰方式解除PEBP 2/CBF的调节。与模拟转染子的活性相比，PEBP 2 β-MYH 11转染子的增殖、迁移和管形成显著降低。这些结果表明，转录因子PEBP 2/CBF在血管生成中起重要作用。
Mice lacking the AML1/PEBP2 alpha B/CBFa2 gene or PEBP2 beta/CBFb gene exhibit a defect in definitive hematopoiesis and die in utero because of hemorrhage in the central nervous system. Hematopoiesis in the embryo is considered to be tightly associated with vascular development, Here ive examined whether PEBP2/CBF plays any role in angiogenesis besides that in definitive hematopoiesis, We found that AML1/ PEBP2 alpha B/CBFa2, PEBP2 alpha A/CBFa1, and PEBP2 beta/ CBFb were expressed in a murine endothelial cell Line MISS31, The expression of these molecules as cell as the DNA binding activity of PEBP2/CBF were augmented by angiogenic growth factors such as bFGF and VEGF. Moreover, the expression of PEBP2 alpha/CBFa protein in endothelial tells was confirmed at the site of angiogenesis in vivo, To further clarify the role of PEBP2/CF in angiogenesis, we established permanent transfectants of PEBP2 beta-MYH11 gene, one that interacts with the runt domain of the alpha subunit and deregulates PEBP2/CBF in a dominant interfering manner. Proliferation, migration, and tube formation of the PEBP2 beta-MYH11 transfectants were significantly reduced in comparison with those activities of the mock transfectants. These results suggest that transcription factor PEBP2/CBF plays an important role in angiogenesis.