| First Author | Mühlner U | Year | 1999 |
| Journal | Oncogene | Volume | 18 |
| Issue | 29 | Pages | 4200-10 |
| PubMed ID | 10435633 | Mgi Jnum | J:156986 |
| Mgi Id | MGI:4422172 | Doi | 10.1038/sj.onc.1203014 |
| Citation | Muhlner U, et al. (1999) Formation of transformed endothelial cells in the absence of VEGFR-2/Flk-1 by Polyoma middle T oncogene. Oncogene 18(29):4200-10 |
| abstractText | The middle T antigen of murine Polyomavirus (PymT) rapidly transforms endothelial cells leading to vascular malformations reminiscent of endothelial tumors or hemangiomas. Flk-1, a receptor tyrosine kinase which is activated upon binding of its ligand VEGF, is predominantly expressed in endothelial cells and essential for the formation of blood vessels since absence of Flk-1 prevents the development of mature endothelial cells in mice and in ES-cell differentiation experiments. To investigate the role of Flk-1 in PymT-induced vascular tumor formation, we studied the expression of Flk-1 and VEGF in PymT-transformed endothelial cells (Endothelioma cells, END. cells). The receptor and its ligand were both expressed in END. cells suggesting that a VEGF/Flk-1 autocrine loop might be causally involved in the formation of vascular tumors. To test this hypothesis, ES cells lacking Flk-1 were generated and the transforming potential of PymT was analysed after in vitro differentiation. Flk-1(-/-) END. cell lines were established which are morphologically identical to flk-1(+/+) END. cells and which express several markers characteristic for endothelial cells. This result suggests that PymT functionally replaces the requirement of Flk-1 in expansion and/or survival of endothelial progenitor cells. Therefore, flk-1(-/-) END. cells provide a powerful tool to dissect the downstream signaling pathways of Flk-1. |
