The contribution of NF-κB activity to spontaneous proliferation and resistance to apoptosis in human T-cell leukemia virus type 1 Tax-induced tumors

Abstract

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)-κB activity to spontaneous tumor cell proliferation and resistance to apoptosis. We have demonstrated elevated expression levels of NF-κB–inducible cytokines, including interleukin (IL)-6, IL-10, IL-15, and interferon (IFN)-γ, in freshly isolated primary tumors from Tax transgenic mice. Inhibitors of NF-κB activity, sodium salicylate and cyclopentenone prostaglandins (prostaglandin A1 and 15-deoxy-Δ(12,14)-prostaglandin J2), 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-κB activity contributes to tumorigenesis in vivo.