title: Kaposi sarcoma-associated herpesvirus-encoded viral FLICE inhibitory protein (vFLIP) K13 cooperates with Myc to promote lymphoma in mice.
abstract: Primary effusion lymphoma (PEL) is an aggressive form of lymphoma that is associated with infection by Kaposi's sarcoma-associated herpesvirus (KSHV). One of the KSHV genes expressed in PEL cells is K13, a potent activator of the NF-κB pathway. K13 transgenic mice develop lymphomas, but after a long period of latency. A possible candidate that could cooperate with K13 in the development of PEL is c-Myc, whose expression is frequently dysregulated in PEL cells. To study the cooperative interaction between K13 and c-Myc in the pathogenesis of PEL, we crossed the K13 transgenic mice to iMyc(Eμ) transgenic mice that overexpress Myc. We report that lymphomas in the K13/iMyc(Eμ) double transgenic mice developed with shorter latency and were histologically distinct from those observed in the iMyc(Eμ) mice. Lymphomas in the K13/iMyc(Eμ) mice also lacked the expression of B- and T-cell markers, thus resembling the immunophenotype of PEL. The accelerated development of lymphoma in the K13/iMyc(Eμ) mice was associated with increased expression of K13, elevated NF-κB activity and decrease in apoptosis. Taken collectively, our results demonstrate a cooperative interaction between the NF-κB and Myc pathways in lymphomagenesis.
authors.affiliation: Department of Medicine, University of Pittsburgh Cancer Institute, PA, USA.
authors.forename: Anwaar
authors.initials: A
authors.lastname: Ahmad
authors.forename: Jason S
authors.initials: JS
authors.lastname: Groshong
authors.forename: Hittu
authors.initials: H
authors.lastname: Matta
authors.forename: Sandra
authors.initials: S
authors.lastname: Schamus
authors.forename: Vasu
authors.initials: V
authors.lastname: Punj
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Robinson
authors.forename: Parkash S
authors.initials: PS
authors.lastname: Gill
authors.forename: Preet M
authors.initials: PM
authors.lastname: Chaudhary
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D005434:Flow Cytometry; D019288:Herpesvirus 8, Human / Q000235:genetics*; D007124:Immunoenzyme Techniques; D054685:Lymphoma, Primary Effusion / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014162:Transfection; D014764:Viral Proteins / Q000502:physiology*
chemical_list: D016328:NF-kappa B; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D014764:Viral Proteins; C481275:viral FLIP protein, Human herpesvirus 8
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