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• W2118322364 startingPage "4994" @default.
• W2118322364 abstract "Understanding the regulation of endothelial cell (EC) gene expression has important implications for angiogenesis, tumor growth, and metastasis. The transcription factor runt-related gene 2 (RUNX2)/core binding factoralpha-1/acute myeloid leukemia 3/polyoma enhancer-binding protein 2alphaA/osteoblast-specific transcription factor 2 regulates osteoblast differentiation, increases lymphomagenesis in transgenic mice, and is expressed in murine ECs. Here, we report on RUNX2 expression in human bone marrow EC (HBME-1) and its role in EC differentiation. Expression of RUNX2 occurred in HBME-1 cultured on extracellular matrix (ECM) substrates that stimulate in vitro differentiation (tube formation). Neutralizing anti-insulin-like growth factor (IGF)-I-receptor antibody inhibited tube formation as well as activation of RUNX2 expression in HBME-1 cultured on ECM. IGF-I treatment also increased both RUNX2 mRNA and protein expression. HBME-1 transfectants expressing dominant-negative (DN) RUNX were established to address the role of RUNX2 in these processes. HBME/DN cells exhibited reduced tube formation activity relative to control transfectants and less ability to growth arrest and differentiate on ECM. DNRUNX expression also inhibited HBME-1 migration and invasion, which are necessary for tube formation. The urokinase-type plasminogen activator and membrane-type MMP-1 genes were consistently down-regulated in DNRUNX transfectants. The results suggest that RUNX2 is important in IGF-I and ECM-regulated EC migration and differentiation. RUNX2 effects on HBME-1 migration and invasion may occur through activation of protease expression, events that regulate angiogenesis, and tumor growth." @default.
• W2118322364 created "2016-06-24" @default.
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• W2118322364 date "2001-07-01" @default.
• W2118322364 modified "2023-09-23" @default.
• W2118322364 title "Runt-related gene 2 in endothelial cells: inducible expression and specific regulation of cell migration and invasion." @default.
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