Kaposi sarcoma-associated herpesvirus-encoded viral FLICE inhibitory protein (vFLIP) K13 cooperates with Myc to promote lymphoma in mice.
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.
Ahmad
Anwaar
A
Department of Medicine, University of Pittsburgh Cancer Institute, PA, USA.
Groshong
Jason S
JS
Matta
Hittu
H
Schamus
Sandra
S
Punj
Vasu
V
Robinson
Lisa J
LJ
Gill
Parkash S
PS
Chaudhary
Preet M
PM
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*
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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