| General information | Literature | Expression | Regulation | Mutation | Interaction |
Basic Information | |
|---|---|
Gene ID | 8743 |
Name | TNFSF10 |
Synonymous | APO2L|Apo-2L|CD253|TL2|TRAIL;tumor necrosis factor (ligand) superfamily, member 10;TNFSF10;tumor necrosis factor (ligand) superfamily, member 10 |
Definition | Apo-2 ligand|TNF-related apoptosis inducing ligand TRAIL|chemokine tumor necrosis factor ligand superfamily member 10|tumor necrosis factor (ligand) family, member 10|tumor necrosis factor apoptosis-inducing ligand splice variant delta|tumor necrosis fact |
Position | 3q26 |
Gene type | protein-coding |
Cancer type | Abstract |
| Ewing's sarcoma ;Bone | Ewing's sarcoma is the second most common human bone tumor in childhood. Here, we investigated the sensitivity of the Ewing tumor cell line, SK-N-MC, to the apoptotic effect of type I (IFNalpha) and type II (IFNgamma) interferons and TNFalpha. We demonstrate that although IFNalpha and TNFalpha alone are unable toinduce cell death, they act in synergy with IFNgamma to induce SK-N-MC cell apoptosis. The synergistic induction of apoptosis correlated with the synergistic induction of TNFalpha-related apoptosis-inducing ligand (TRAIL) mRNA and TRAIL protein synthesis as well as of TRAIL secretion. Preparations of inducer-free supernatants from SK-N-MC cells stimulated with combinations of cytokines were shown to be cytotoxic for untreated SK-N-MC cells. This cytotoxicity was partially inhibited by addition of TRAILR2/Fc fusion protein, indicating that the secreted TRAIL mediates, at least in part, the apoptotic effect displayed by thesupernatants of stimulated SK-N-MC cells. We have shown that the presence of IFNgamma is required to allow the sustained expression of IRF1 in SK-N-MC cells stimulated by addition of IFNalpha or TNFalpha suggesting that IRF1 plays a rolein the synergistic induction of apoptosis by combinations of cytokines. Furthermore, we have shown that inhibition of NF-kappaB activation contributes to the IFNgamma-mediated sensitization to the apoptotic effect of TNFalpha. To our knowledge, this is the first report showing that interferon/cytokine combinations are able to induce TRAIL gene expression and TRAIL protein synthesis and secretion in Ewing sarcoma-derived cells. We believe that the observations reported here might contribute to the development of alternative new approaches to the treatment of Ewing tumors resistant to conventional therapy.#CI- Copyright 2004 Nature Publishing Group |