The contribution of NF-κB 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)-kappaB activity to spontaneous tumor cell proliferation and resistance to apoptosis. We have demonstrated elevated expression levels of NF-kappaB-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-kappaB 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-kappaB activity contributes to tumorigenesis in vivo.