Abstract | BACKGROUND: The K1 gene of human herpesvirus-8 (HHV-8; also known as Kaposi's sarcoma-associated herpesvirus) encodes a transmembrane signaling protein that elicits cellular activation events. To evaluate the potential role of K1 in HHV-8-associated pathogenesis, we produced transgenic mice expressing the HHV-8 K1 gene under the transcriptional control of the simian virus 40 promoter. METHODS: RESULTS: Expression of bFGF was increased in K1-transgenic mice as compared with nontransgenic mice, whereas expression of TNF-alpha and IL-6 did not differ using reverse transcriptase-polymerase chain reaction. K1-transgenic mice showed substantially less serum IL-12 induction than did nontransgenic mice when challenged with a lipopolysaccharide. B lymphocytes from K1-transgenic mice but not from nontransgenic mice showed constitutive activation of NF-kappaB and Oct-2. K1 expression in human B lymphocytes stimulated NF-kappaB-dependent promoter activity. B lymphocytes from K1-transgenic mice also showed increased phosphorylation of Lyn, a Src family tyrosine kinase, and enhanced Lyn activity. Tumors in K1-transgenic mice showed features indicative of a spindle-cell sarcomatoid tumor and a malignant plasmablastic lymphoma. The pattern of cytokine, transcription factor, and Lyn kinase activity in the lymphoma was similar to that in B lymphocytes from K1-transgenic mice. CONCLUSION: K1 may be involved in the activation of NF-kappaB signaling. The enhanced NF-kappaB activity in nonmalignant lymphocytes of K1 mice and its persistence in lymphoma tumors of these mice suggest that the K1 mouse may be a model of premalignancy.
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Authors | Om Prakash, Zhen-Ya Tang, Xiaochang Peng, Roy Coleman, Javed Gill, Gist Farr, Felipe Samaniego |
Journal | Journal of the National Cancer Institute
(J Natl Cancer Inst)
Vol. 94
Issue 12
Pg. 926-35
(Jun 19 2002)
ISSN: 0027-8874 [Print] United States |
PMID | 12072546
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Cytokines
- DNA Primers
- Glycoproteins
- K1 protein, Human herpesvirus 8
- RNA, Messenger
- Viral Proteins
- Interleukin-12
- Protein-Tyrosine Kinases
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Topics |
- Animals
- B-Lymphocytes
(immunology)
- Cytokines
(genetics)
- DNA Primers
- Enzyme Activation
- Glycoproteins
(genetics, metabolism)
- Herpesviridae Infections
(virology)
- Herpesvirus 8, Human
(genetics)
- Humans
- Interleukin-12
(genetics)
- Lymphoma
(genetics, pathology, virology)
- Mice
- Mice, Transgenic
- Protein-Tyrosine Kinases
(metabolism)
- RNA, Messenger
(genetics)
- Reverse Transcriptase Polymerase Chain Reaction
- T-Lymphocytes
(immunology)
- Viral Proteins
(genetics, metabolism)
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