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A new model of LMP1-MYC interaction in B cell lymphoma. Leuk Lymphoma 2014 Dec;55(12):2917-23

Date

03/13/2014

Pubmed ID

24605938

Pubmed Central ID

PMC4207734

DOI

10.3109/10428194.2014.900762

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.

Author List

Ontiveros EP, Halwani A, Stunz LL, Kamberos N, Olivier AK, Janz S, Bishop GA

Author

Siegfried Janz MD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Cell Line, Tumor
Disease Models, Animal
Gene Expression
Genotype
Immunophenotyping
Interleukin-6
Lymphoma, B-Cell
Mice
Mice, Transgenic
Phenotype
Prognosis
Proto-Oncogene Proteins c-myc
Proto-Oncogene Proteins c-pim-1
Signal Transduction
Viral Matrix Proteins
jenkins-FCD Prod-403 0f9a74600e4e79798f8fa6f545ea115f3dd948b2