Regulation of endothelial cell differentiation and transformation by H-Ras
2003 (English)In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 291, no 1, 189-200 p.Article in journal (Refereed) Published
Angiogenesis is regulated by growth factors which activate tyrosine kinase receptors leading to the activation of a number of intracellular signaling pathways. The specific function of H-Ras during FGF-2 stimulated endothelial cell differentiation, defined as invasive growth and formation of branching networks in fibrin gels, was investigated by using conditionally immortalized endothelial cell lines induced to express H-Ras mutants. Expression of inhibitory N17Ras did not impair differentiation in response to FGF-2 and TNF-alpha. The farnesyltransferase inhibitor FTI-277 inhibited farnesylation of Ras but did not inhibit differentiation of human microvascular endothelial cells or mouse brain endothelial cells. In contrast, activated V12Ras inhibited endothelial cell differentiation and cells displayed a transformed phenotype with an increased rate of proliferation and loss of contact inhibited growth. Furthermore, V12Ras expressing endothelial cells grew as solid tumors when injected subcutaneously into mice. Our data suggest that, in endothelial cells, H-Ras activity is not required for differentiation. However, this activity must be tightly regulated as aberrant activity can disturb the ability of endothelial cells to undergo differentiation.
Place, publisher, year, edition, pages
2003. Vol. 291, no 1, 189-200 p.
Endothelium, Differentiation, Transformation, Proliferation, Ras, FGF-2, Angiogenesis, Tumor, Angiosarcoma
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-91472DOI: 10.1016/S0014-4827(03)00347-1PubMedID: 14597419OAI: oai:DiVA.org:uu-91472DiVA: diva2:164211