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American Journal of Pathology, Vol 149, 945-952, Copyright © 1996 by American Society for Investigative Pathology

REGULAR ARTICLES

Tumor-necrosis-factor-induced fibroblast growth factor-1 acts as a survival factor in a transformed endothelial cell line

JA Maier, D Morelli, S Menard, MI Colnaghi and A Balsari
Department of Biomedical Sciences and Technologies, Ospedale San Raffaele, Milan, Italy.

Endothelial cells undergo apoptosis after withdrawal of growth factors, alterations in the extracellular matrix, or exposure to cytokines. Here we report that tumor necrosis factor (TNF)-alpha induces apoptosis of human endothelial cells derived from the umbilical vein in a dose- 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 endothelial cells. This proliferative effect is mediated through the up- regulation of fibroblast growth factor-1 by TNF. The addition of specific fibroblast growth factor-1 antisense oligonucleotides inhibits TNF-induced fibroblast growth factor-1 expression, thus inhibiting the growth and triggering apoptosis of spontaneously transformed human umbilical vein endothelial cells.

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