Abstract |
Epstein-Barr virus (EBV) is a lymphotrophic herpesvirus infecting most of the world's population. It is associated with a number of human lymphoid and epithelial tumors and lymphoproliferative diseases in immunocompromised patients. A subset of latent EBV antigens is required for immortalization of primary B-lymphocytes. The metastatic suppressor Nm23-H1 which is downregulated in human invasive breast carcinoma reduces the migration and metastatic activity of breast carcinoma cells when expressed from a heterologous promoter. Interestingly, the EBV nuclear antigen 3C (EBNA3C) reverses these activities of Nm23-H1. The alpha V integrins recognize a variety of ligands for signaling and are involved in cell migration and proliferation and also serve as major receptors for extracellular-matrix-mediated cell adhesion and migration. The goal of this study was to determine if Nm23-H1 and EBNA3C can modulate alpha V integrin expression and downstream activities. The results of our studies indicate that Nm23-H1 downregulates alpha V intregrin expression in a dose responsive manner. In contrast, EBNA3C can upregulate alpha V integrin expression. Furthermore, the study showed that the association of the Sp1 and GATA transcription factors with Nm23-H1 is required for modulation of the alpha V integrin activity. Thus, these results suggest a direct correlation between the alpha V integrin expression and the interaction of Nm23-H1 with EBNA3C.
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Authors | Tathagata Choudhuri, Subhash C Verma, Ke Lan, Erle S Robertson |
Journal | Virology
(Virology)
Vol. 351
Issue 1
Pg. 58-72
(Jul 20 2006)
ISSN: 0042-6822 [Print] United States |
PMID | 16631833
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Antigens, Viral
- EBNA-3C, epstein-barr virus
- Epstein-Barr Virus Nuclear Antigens
- GATA1 Transcription Factor
- GATA1 protein, human
- Integrin alphaV
- NM23 Nucleoside Diphosphate Kinases
- Sp1 Transcription Factor
- NME1 protein, human
- Nucleoside-Diphosphate Kinase
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Topics |
- Antigens, Viral
(genetics, metabolism)
- B-Lymphocytes
(metabolism)
- Cell Line, Tumor
- Cell Movement
- Cell Proliferation
- Down-Regulation
- Epstein-Barr Virus Nuclear Antigens
- GATA1 Transcription Factor
(metabolism)
- Gene Expression Regulation
- Humans
- Integrin alphaV
(genetics, metabolism)
- NM23 Nucleoside Diphosphate Kinases
- Nucleoside-Diphosphate Kinase
(genetics, metabolism)
- Promoter Regions, Genetic
- Sp1 Transcription Factor
(metabolism)
- Transcription, Genetic
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