TUMOR-NECROSIS-FACTOR-INDUCED FIBROBLAST GROWTH-FACTOR-I ACTS AS A SURVIVAL FACTOR IN A TRANSFORMED ENDOTHELIAL-CELL LINE

Endothelial cells undergo apoptosis after with-drawal of growth factor s, alterations in the extracellular matrix, or exposure to cytokines. Here toe report that tumor necrosis factor (TNF)-alpha induces apoptos is of human endothelial cells derived from the umbilical vein in a dos e-dependent fashion, Apoptosis is triggered through a pathway that is independent from the levels of Bcl-2. On the contrary, TNF stimulates the growth of spontaneously transformed human umbilical vein endotheli al cells. This proliferative effect is mediated through the up-regulat ion of fibroblast growth factor-1 by TNF. The addition of specific fib roblast growth factor-1 antisense oligonucleotides inhibits TNF-induce d fibroblast growth factor-1 expression, thus inhibiting the growth an d triggering apoptosis of spontaneously transformed human umbilical ve in endothelial cells.