The Role of Ets Factors in Tumor Angiogenesis

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.