Inhibition of constitutive NF-kappa B activity suppresses tumorigenicity of Ewing sarcoma EW7 cells.
Ewing sarcoma is 1 of the most aggressive tumors that can affect children and young adults. Despite advances in therapy, the prognosis remains poor emphasizing the need for defining new targets for treatment. We investigated a possible role of nuclear factor-kappa B (NF-kappa B) activity of Ewing sarcoma-derived EW7 cells in their tumorigenicity. In these cells, expression of a degradation-resistant form of the inhibitory factor I kappa B alpha inhibited NF-kappa B activity without affecting their in vitro proliferation rate. It causes, however, a remarkable loss of their ability to generate tumors in nude mice that correlates with both a decrease in extracellular matrix (ECM) protein secretion and an acquisition of sensitivity to murine tumor necrosis factor alpha (TNF alpha)-induced apoptosis. These data support the concept that NF-kappa B activity plays a role in the tumorigenicity of Ewing sarcoma cells, identifying NF-kappa B as a potential target for reducing Ewing tumor progression.
Javelaud
Delphine
D
Institut National de la Santé et de la Recherche Médicale, U 365, Institut Curie, Paris, France.
Poupon
Marie-France
MF
Wietzerbin
Juana
J
Besançon
Françoise
F
D043925:Angiogenesis Inducing Agents / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D001859:Bone Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D020672:I-kappa B Proteins; D007700:Kinetics; D051379:Mice; D008819:Mice, Nude; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology; D012334:RNA, Neoplasm / Q000096:biosynthesis; D012512:Sarcoma, Ewing / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D043925:Angiogenesis Inducing Agents; D004268:DNA-Binding Proteins; D016326:Extracellular Matrix Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D012334:RNA, Neoplasm; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha