EBV latent membrane protein 1 activates Akt, NFkappaB, and Stat3 in B cell lymphomas.
Latent membrane protein 1 (LMP1) is the major oncoprotein of Epstein-Barr virus (EBV). In transgenic mice, LMP1 promotes increased lymphoma development by 12 mo of age. This study reveals that lymphoma develops in B-1a lymphocytes, a population that is associated with transformation in older mice. The lymphoma cells have deregulated cell cycle markers, and inhibitors of Akt, NFkappaB, and Stat3 block the enhanced viability of LMP1 transgenic lymphocytes and lymphoma cells in vitro. Lymphoma cells are independent of IL4/Stat6 signaling for survival and proliferation, but have constitutively activated Stat3 signaling. These same targets are also deregulated in wild-type B-1a lymphomas that arise spontaneously through age predisposition. These results suggest that Akt, NFkappaB, and Stat3 pathways may serve as effective targets in the treatment of EBV-associated B cell lymphomas.
Shair
Kathy H Y
KH
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Bendt
Katherine M
KM
Edwards
Rachel H
RH
Bedford
Elisabeth C
EC
Nielsen
Judith N
JN
Raab-Traub
Nancy
N
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000378:metabolism / Q000821:virology; D001402:B-Lymphocytes / Q000378:metabolism / Q000821:virology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human; D015151:Immunoblotting; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000821:virology*; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; D014763:Viral Matrix Proteins; D051057:Proto-Oncogene Proteins c-akt