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Kaposi's sarcoma-like tumors in a human herpesvirus 8 ORF74 transgenic mouse
- Source :
- Journal of virology. 77(4)
- Publication Year :
- 2003
-
Abstract
- The product of human herpesvirus 8 (HHV-8) open reading frame 74 (ORF74) is related structurally and functionally to cellular chemokine receptors. ORF74 activates several cellular signaling pathways in the absence of added ligands, and NIH 3T3 cells expressing ORF74 are tumorigenic in nude mice. We have generated a line of transgenic (Tg) mice with ORF74 driven by the simian virus 40 early promoter. A minority (approximately 30%) of the Tg mice, including the founder, developed tumors resembling Kaposi's sarcoma (KS) lesions, which occurred most typically on the tail or legs. The tumors were highly vascularized, had a spindle cell component, expressed VEGF-C mRNA, and contained a majority of CD31 + cells. CD31 and VEGF-C are typically expressed in KS. Tumors generally (but not always) occurred at single sites and most were relatively indolent, although several mice developed large visceral tumors. ORF74 was expressed in a minority of cells in the Tg tumors and in a few other tissues of mice with tumors; mice without tumors did not express detectable ORF74 in any tissues tested. Cell lines established from tumors expressed ORF74 in a majority of cells, expressed VEGF-C mRNA, and were tumorigenic in nude mice. The resultant tumors grew rapidly, metastasized, and continued to express ORF74. Cell lines established from these secondary tumors also expressed ORF74 and were tumorigenic. These data strongly suggest that ORF74 plays a role in the pathology of KS and confirm and extend previous findings on the tumorigenic potential of ORF74.
- Subjects :
- Genetically modified mouse
CD31
Male
Transgene
Immunology
Mice, Transgenic
Biology
Microbiology
3T3 cells
Chemokine receptor
Mice
Viral Proteins
Virology
medicine
Tumor Cells, Cultured
Animals
Transgenes
Kaposi's sarcoma
Sarcoma, Kaposi
medicine.disease
Immunohistochemistry
Mice, Inbred C57BL
medicine.anatomical_structure
Insect Science
Herpesvirus 8, Human
Cancer research
Pathogenesis and Immunity
Female
Receptors, Chemokine
Sarcoma
Subjects
Details
- ISSN :
- 0022538X
- Volume :
- 77
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Journal of virology
- Accession number :
- edsair.doi.dedup.....5780fb887399cd7ea3e853c5fd0de777