Kaposi's sarcoma associated herpesvirus-encoded viral FLICE inhibitory protein (vFLIP) K13 cooperates with Myc to promote lymphoma in mice.
Summary of "Kaposi's 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 NFkappaB 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(Emu) transgenic mice that overexpress Myc. We report that lymphomas in the K13/iMyc(Emu) double transgenic mice developed with shorter latency and were histologically distinct from those observed in the iMyc(Emu) mice. Lymphomas in the K13/iMyc(Emu) 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(Emu) mice was associated with increased expression of K13, elevated NFkappaB activity and decrease in apoptosis. Taken collectively, our results demonstrate a cooperative interaction between the NFkappaB and Myc pathways in lymphomagenesis.
Affiliation
Department of Medicine, Division of Hematology-Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
Journal Details
This article was published in the following journal.
Name: Cancer biology & therapy
ISSN: 1555-8576
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20818173
- DOI: http://dx.doi.org/10.4161/cbt.10.10.13291
Medical and Biotech [MESH] Definitions
Kaposi Varicelliform Eruption
A disseminated vesicular-pustular eruption caused by the herpes simplex virus (HERPESVIRUS HOMINIS), the VACCINIA VIRUS, or Varicella zoster (HERPESVIRUS 3, HUMAN). It is usually superimposed on a preexisting, inactive or active, atopic dermatitis (DERMATITIS, ATOPIC).
Herpesvirus 8, Human
A species in the genus RHADINOVIRUS, subfamily GAMMAHERPESVIRINAE, isolated from patients with AIDS-related and "classical" Kaposi sarcoma.
Epstein-barr Virus Nuclear Antigens
Nuclear antigens encoded by VIRAL GENES found in HUMAN HERPESVIRUS 4. At least six nuclear antigens have been identified.
Marek Disease
A transmissible viral disease of birds caused by avian herpesvirus 2 (HERPESVIRUS 2, GALLID) and other MARDIVIRUS. There is lymphoid cell infiltration or lymphomatous tumor formation in the peripheral nerves and gonads, but may also involve visceral organs, skin, muscle, and the eye.
Adenovirus Early Proteins
Proteins encoded by adenoviruses that are synthesized prior to, and in the absence of, viral DNA replication. The proteins are involved in both positive and negative regulation of expression in viral and cellular genes, and also affect the stability of viral mRNA. Some are also involved in oncogenic transformation.
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