ebv latent membrane protein 1 activates akt, nfκb, and stat3 in b cell lymphomasebv潜伏膜蛋白1 akt,nfκb,stat3在b细胞淋巴瘤.pdfVIP

EBV Latent Membrane Protein 1 Activates Akt, NFjB, and Stat3 in B Cell Lymphomas 1 1 1 1 2 Kathy H. Y. Shair , Katherine M. Bendt , Rachel H. Edwards , Elisabeth C. Bedford , Judith N. Nielsen , Nancy Raab-Traub1,3* 1 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, 2 Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, 3 Department of Microbiology-Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America 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, NFjB, 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, NFjB, and Stat3 pathways may serve as effective targets in the treatment of EBV-associated B cell lymphomas. Citation: Shair KHY, Bendt KM, Edwards RH, Bedford EC, Nielsen JN, et al. (2007) EBV latent membrane protein 1 activates Akt, NFjB, and Stat3 in B cell lymphomas. PLoS Pathog 3(11): e166. doi:10.1371/journal.ppat.0030166 Introduction