NF-kappa B is essential for the progression of KSHV- and EBV-infected lymphomas in vivo Journal Article
| Authors: | Keller, S. A.; Hernandez-Hopkins, D.; Vider, J.; Ponomarev, V.; Hyjek, E.; Schattner, E. J.; Cesarman, E. |
| Article Title: | NF-kappa B is essential for the progression of KSHV- and EBV-infected lymphomas in vivo |
| Abstract: | Activated NF-kappa B is a critical mechanism by which lymphoma cells infected by Epstein-Barr virus (EBV/HHV-4) and Kaposi sarcoma herpesvirus (KSHV/HHV-8) are protected from apoptotic stress. Selective pharmacologic inhibition of constitutive NF-kappa B activity induces apoptosis in KSHV- and EBV-infected lymphoma cells. In both tumor types, pharmacologic inhibition of NF-kappa B in vitro induced identical mitochondrially mediated apoptosis cascades. Assessment of gene regulation by microarray analysis revealed that the inhibition of NF-kappa B in tumor cells results in the down-regulation of a distinct group of prosurvival genes, including clAP-1, cIAP-2, cFLIP, and IL-6. Using EBV- and KSHV-associated lymphomas in a murine system, we demonstrated that Bay 117082, a selective pharmacologic inhibitor of NF-kappa B prevents or delays tumor growth and prolongs disease-free survival. Inhibition of NF-kappa B activity and tumor growth responses were further documented using a traceable reporter KSHV-positive cell line and in vivo imaging. These findings indicate that specific NF-kappa B-regulated survival factors work cooperatively to protect KSHV- and EBV-infected lymphoma cells from apoptosis such that they promote the establishment and progression of KSHV- and EBV-associated lymphomas in mice. They also support the use of selective NF-kappa B inhibitors in the treatment of herpesvirus-associated lymphomas. |
| Keywords: | apoptosis; death; lymphoproliferative disease; expression; cells; growth; pathway; primary effusion lymphoma; sarcoma-associated herpesvirus; barr-virus; latency |
| Journal Title: | Blood |
| Volume: | 107 |
| Issue: | 8 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2006-04-15 |
| Start Page: | 3295 |
| End Page: | 3302 |
| Language: | English |
| ACCESSION: | WOS:000236833500049 |
| DOI: | 10.1182/blood-2005-07-2730 |
| PROVIDER: | wos |
| PMCID: | PMC1432097 |
| PUBMED: | 16380446 |
| Notes: | --- - Article - "Source: Wos" |
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