Regulation of tumor angiogenesis by transcription factor LMO2

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LMO2 is activated by the chromosomal translocation associated with T cell lymphoblastic leukemia. We have studied the physiological role of LMO2 in the mouse development of hematnpoietic organ using gene targeting study. It revealed that LMO2 is necessary for the initiation of yolk sac erythropoiesis and adult hematopoiesis. This protein is also needed in the process of angiogenesis, although it is dispensable in vasculogenesis. LMO2 is composed of two tandemly repeated LIM domains which play important roles in protein-protein interactions. We think the LMO2 complex including TAL1, LDB1 and GATA1/2/3 is particularly important one in the process of fetal liver hematopoiesis and angiogenesis. LMO2 is used in the complex as the bridging molecule between TAL1, LDB1 and GATA1/2/3, in which N-terminal LIM domain (LIM1) is used in the interactions of LMO2 between TAL1 and LDB1, and C-terminal LIMdomain (LIM2) is used in those of LMO2 and GATA1/2/3.Neovascularization in the process of tumor growth in adult is considered to have the similar mechanism as embryonic angiogenesis. We observed the growth of vascular system in teratocarcinoma by injecting LMO2 null ES cells in mouse subcutaneous dorsa and compared it with the wild type ES cells. Without LMO2, mature blood vessels did not grow in the teratocarcinoma. This results suggest that LMO2 is also important in the tumor neovasuculization. We also studied the expression pattern of the transcription factors which are proved to be important in embryonic angiogenesis in human renal cell carcinoma. LMO2, TAL1, and ID1 was specifically expressed in the endothelium in the renal cell carcinoma. These factors are involved in tumor angiogenesis by up-regulating FLK1, which is the receptor of vascular endothelial growthfactor(VEGF).