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.

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)-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)

• Authors: T Portis, J C Harding, L Ratner
• Journal: Blood (Blood) Vol. 98 Issue 4 Pg. 1200-8 (Aug 15 2001) ISSN: 0006-4971 [Print] United States
• PMID: 11493471 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cytokines
• Gene Products, tax
• NF-kappa B
• Prostaglandins A
• Sodium Salicylate

Topics

• Animals
• Apoptosis (drug effects)
• Cytokines (analysis, metabolism)
• Disease Models, Animal
• Gene Products, tax (genetics, pharmacology)
• Human T-lymphotropic virus 1 (chemistry)
• Humans
• Leukemia-Lymphoma, Adult T-Cell (chemically induced, metabolism, pathology)
• Lymphocyte Activation (drug effects)
• Mice
• Mice, Transgenic
• NF-kappa B (metabolism, pharmacology)
• Prostaglandins A (pharmacology)
• Rats
• Sodium Salicylate (pharmacology)
• Tissue Distribution