title: 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 Eμ enhancer (iMyc(Eμ)), 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(Eμ) mice trended toward earlier BCL onset. BCLs from mCD40-LMP1/iMyc(Eμ) mice expressed LMP1 and were transplantable into immunocompetent recipients. iMyc(Eμ) and mCD40-LMP1/iMyc(Eμ) 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.
authors.affiliation: Department of Microbiology.
authors.forename: Evelena P
authors.initials: EP
authors.lastname: Ontiveros
authors.forename: Ahmad
authors.initials: A
authors.lastname: Halwani
authors.forename: Laura L
authors.initials: LL
authors.lastname: Stunz
authors.forename: Natalie
authors.initials: N
authors.lastname: Kamberos
authors.forename: Alicia K
authors.initials: AK
authors.lastname: Olivier
authors.forename: Siegfried
authors.initials: S
authors.lastname: Janz
authors.forename: Gail A
authors.initials: GA
authors.lastname: Bishop
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015870:Gene Expression; D005838:Genotype; D016130:Immunophenotyping; D015850:Interleukin-6 / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism*; D051573:Proto-Oncogene Proteins c-pim-1 / Q000378:metabolism; D015398:Signal Transduction; D014763:Viral Matrix Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D015850:Interleukin-6; D016271:Proto-Oncogene Proteins c-myc; D014763:Viral Matrix Proteins; D051573:Proto-Oncogene Proteins c-pim-1
keywords: LMP1; MYC; lymphoma