title: Runt-related gene 2 in endothelial cells: inducible expression and specific regulation of cell migration and invasion.
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.
authors: Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors: L
authors: L
authors: Sun
authors: M
authors: M
authors: Vitolo
authors: A
authors: A
authors: Passaniti
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D002417:Cattle; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics*; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit; D050657:Core Binding Factor alpha Subunits; D018076:DNA, Complementary / Q000235:genetics; D010450:Endopeptidases / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D009363:Neoplasm Proteins; D018919:Neovascularization, Physiologic / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D050657:Core Binding Factor alpha Subunits; D018076:DNA, Complementary; D009363:Neoplasm Proteins; D014157:Transcription Factors; D007334:Insulin-Like Growth Factor I; D010450:Endopeptidases