The contribution of NF-kappa B activity to spontaneous proliferation and resistance to apoptosis in human T-cell leukemia virus type 1 Tax-induced tumors.
Human T-cell leukemia virus type I is the etiologic agent of adult T-cell leukemia/lymphoma. The Tax protein of this virus is thought to contribute to cellular transformation and tumor development. In this report, we have used a Tax transgenic mouse model of tumorigenesis to study the contribution of nuclear factor (NF)-kappa B activity to spontaneous tumor cell proliferation and resistance to apoptosis. We have demonstrated elevated expression levels of NF-kappa B--inducible cytokines, including interleukin (IL)-6, IL-10, IL-15, and interferon (IFN)-gamma, in freshly isolated primary tumors from Tax transgenic mice. Inhibitors of NF-kappa B activity, sodium salicylate and cyclopentenone prostaglandins (prostaglandin A(1) and 15-deoxy-Delta(12,14)-prostaglandin J(2)), blocked spontaneous proliferation of Tax transgenic mouse spleen cells. In addition, Tax-induced tumor cells, which are resistant to irradiation-induced apoptosis, became sensitive to apoptosis in the presence of sodium salicylate and prostaglandins. These results strongly suggest that Tax-mediated induction of NF-kappa B activity contributes to tumorigenesis in vivo. (Blood. 2001;98:1200-1208)
Portis
T
T
Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
Harding
J C
JC
Ratner
L
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D004195:Disease Models, Animal; D016356:Gene Products, tax / Q000235:genetics / Q000494:pharmacology*; D015368:Human T-lymphotropic virus 1 / Q000737:chemistry; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism* / Q000494:pharmacology; D011454:Prostaglandins A / Q000494:pharmacology; D051381:Rats; D012980:Sodium Salicylate / Q000494:pharmacology; D014018:Tissue Distribution
D016207:Cytokines; D016356:Gene Products, tax; D016328:NF-kappa B; D011454:Prostaglandins A; D012980:Sodium Salicylate