| First Author | Iwatsuki K | Year | 2005 |
| Journal | Oncogene | Volume | 24 |
| Issue | 7 | Pages | 1129-37 |
| PubMed ID | 15592512 | Mgi Jnum | J:96096 |
| Mgi Id | MGI:3529397 | Doi | 10.1038/sj.onc.1208287 |
| Citation | Iwatsuki K, et al. (2005) Runx1 promotes angiogenesis by downregulation of insulin-like growth factor-binding protein-3. Oncogene 24(7):1129-37 |
| abstractText | Mouse embryos lacking the Runx1 transcription factor exhibit an angiogenic defect accompanied by the absence of hematopoietic stem cells (HSCs). To ask whether Runx1 plays a direct role in angiogenesis, we established a novel endothelial progenitor cell line, designated AEL-DeltaR1, from the aorta-gonad-mesonephros (AGM) region of Runx1-null mouse. We introduced Runx1 cDNA into AEL-DeltaR1 cells under the doxycycline-inducible promoter. The ability of AEL-DeltaR1 cells to form vascular networks on matrigel was highly enhanced by the restored expression of Runx1. By molecular comparison of mRNAs in AEL-DeltaR1 cells before and after the induction of Runx1, we found that mRNA expression of insulin-like growth factor-binding protein 3 (IGFBP-3) is downregulated by Runx1. Gel retardation and reporter assays revealed that Runx1 binds to the promoter region of mouse IGFBP-3 gene and represses its transcription. When IGFBP-3 was exogenously added in the matrigel assay, the angiogenesis-enhancing activity of Runx1 was suppressed in a dose-dependent manner. These results demonstrate that Runx1 is directly involved in angiogenesis by repression of IGFBP-3 mRNA expression. |
