A new model of LMP1-MYC interaction in B cell lymphoma.

ABSTRACT: Epstein-Barr virus (EBV) is associated with aggressive B cell lymphomas (BCLs). Latent membrane protein 1 (LMP1) of EBV is an oncogenic protein required for EBV B cell transformation. However, LMP1 is a weak oncogene in mice. Mice expressing Myc inserted 5' of the E? enhancer (iMyc(E?)), mimicking the t(8;14) translocation of endemic Burkitt lymphoma, develop delayed onset BCLs. To investigate potential cooperation between LMP1 and oncogenic MYC, we produced mice expressing the LMP1 signaling domain via a hybrid CD40-LMP1 transgene (mCD40-LMP1), and the dysregulated MYC protein of aggressive EBV+ BCLs. mCD40-LMP1/iMyc(E?) mice trended toward earlier BCL onset. BCLs from mCD40-LMP1/iMyc(E?) mice expressed LMP1 and were transplantable into immunocompetent recipients. iMyc(E?) and mCD40-LMP1/iMyc(E?) mice developed BCLs with similar immunophenotypes. LMP1 signaling was intact in BCLs as shown by inducible interleukin-6. Additionally, LMP1 signaling to tumor cells induced the two isoforms of Pim1, a constitutively active prosurvival kinase implicated in lymphomagenesis.

SUBMITTER: Ontiveros EP 

PROVIDER: S-EPMC4207734 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature