Tumor-necrosis-factor-induced fibroblast growth factor-1 acts as a survival factor in a transformed endothelial cell line.
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.
Maier
J A
JA
Department of Biomedical Sciences and Technologies, Ospedale San Raffaele, Milan, Italy.
Morelli
D
D
Ménard
S
S
Colnaghi
M I
MI
Balsari
A
A
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation / Q000502:physiology*
C100666:KCB-1 protein, recombinant; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2