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.
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.
Mesh Terms:
Antigens, Viral, B-Lymphocytes, Cell Line, Tumor, Cell Movement, Cell Proliferation, Down-Regulation, GATA1 Transcription Factor, Gene Expression Regulation, Humans, Integrin alphaV, NM23 Nucleoside Diphosphate Kinases, Nucleoside-Diphosphate Kinase, Promoter Regions, Genetic, Sp1 Transcription Factor, Transcription, Genetic
Antigens, Viral, B-Lymphocytes, Cell Line, Tumor, Cell Movement, Cell Proliferation, Down-Regulation, GATA1 Transcription Factor, Gene Expression Regulation, Humans, Integrin alphaV, NM23 Nucleoside Diphosphate Kinases, Nucleoside-Diphosphate Kinase, Promoter Regions, Genetic, Sp1 Transcription Factor, Transcription, Genetic
Virology
Date: Jul. 20, 2006
PubMed ID: 16631833
View in: Pubmed Google Scholar
Download Curated Data For This Publication
108567
Switch View:
- Interactions 1