EBV Latent Membrane Protein 1 Activates Akt, NFκB, and Stat3 in B Cell Lymphomas

PLoS Pathogens

Judith N Nielsen¹  Nancy Raab-Traub²  Rachel H Edwards²  Elisabeth C Bedford²  Katherine M Bendt²  Kathy H. Y Shair² 

[1] Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America;Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America

关键词: Lymphomas;    B cells;    Lymphocytes;    Lymphoma cells;    Mouse models;    STAT signaling;    Flow cytometry;    Spleen;   

DOI  :  10.1371/journal.ppat.0030166

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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, NFκB, 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, NFκB, and Stat3 pathways may serve as effective targets in the treatment of EBV-associated B cell lymphomas.

【 授权许可】

CC BY