Division of Cardiology, and Molecular and Vascular Biology, Department of Medicine, Research North RM 270D, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02115, USA.
J Oncol. 2010;2010:767384. doi: 10.1155/2010/767384. Epub 2010 May 4.
Angiogenesis is a critical component of tumor growth. A number of growth factors, including VEGF, FGF, and HGF, have been implicated as angiogenic growth factors that promote tumor angiogenesis in different types of cancer. Ets-1 is the prototypic member of the Ets transcription factor family. Ets-1 is known to be a downstream mediator of angiogenic growth factors. Expression of Ets-1 in a variety of different tumors is associated with increased angiogenesis. A role for other selected members of the Ets transcription factor family has also been shown to be important for the development of tumor angiogenesis. Because Ets factors also express a number of other important genes involved in cell growth, they contribute not only to tumor growth, but to disease progression. Targeting Ets factors in mouse tumor models through the use of dominant-negative Ets proteins or membrane permeable peptides directed at competitively inhibiting the DNA binding domain has now demonstrated the therapeutic potential of inhibiting selected Ets transcription factors to limit tumor growth and disease progression.
血管生成是肿瘤生长的关键组成部分。许多生长因子,包括 VEGF、FGF 和 HGF,都被认为是血管生成生长因子,它们促进不同类型癌症的肿瘤血管生成。Ets-1 是 Ets 转录因子家族的典型成员。Ets-1 是已知的血管生成生长因子的下游介质。Ets-1 在各种不同肿瘤中的表达与血管生成增加有关。其他选定的 Ets 转录因子家族成员的作用也被证明对肿瘤血管生成的发展很重要。因为 Ets 因子还表达许多其他与细胞生长有关的重要基因,它们不仅有助于肿瘤生长,还有助于疾病进展。通过使用显性负 Ets 蛋白或针对竞争性抑制 DNA 结合域的膜渗透肽在小鼠肿瘤模型中靶向 Ets 因子,现已证明抑制选定的 Ets 转录因子以限制肿瘤生长和疾病进展具有治疗潜力。