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Expression of alpha V integrin is modulated by Epstein-Barr virus nuclear antigen 3C and the metastasis suppressor Nm23-H1 through interaction with the GATA-1 and Sp1 transcription factors.

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.
AuthorsTathagata Choudhuri, Subhash C Verma, Ke Lan, Erle S Robertson
JournalVirology (Virology) Vol. 351 Issue 1 Pg. 58-72 (Jul 20 2006) ISSN: 0042-6822 [Print] United States
PMID16631833 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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
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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