Insights into Gene Expression Changes Impacting B-cell Transformation: Cross-species Microarray Analysis of Bovine Leukemia Virus Tax-responsive Genes in Ovine B Cells.
From: Laboratory of Experimental Hematology, Bordet Institute, 121 Blvd. de Waterloo, 1000 Brussels, Belgium.
Journal of virology
- Publish Date: Feb 2006
- ISSN: 0022-538X
- Volume: 80
- Issue: 4
- Pages: 1922-38
- Medium: Print
- Language: English
- Citation (JAMA): Klener Pavel, Szynal Maud, Cleuter Yvette, et al. Insights into Gene Expression Changes Impacting B-cell Transformation: Cross-species Microarray Analysis of Bovine Leukemia Virus Tax-responsive Genes in Ovine B Cells.. J. Virol. Feb 2006;80:1922-38
Abstract
Large-animal models for leukemia have the potential to aid in the understanding of networks that contribute to oncogenesis. Infection of cattle and sheep with bovine leukemia virus (BLV), a complex retrovirus related to human T-cell leukemia virus type 1 (HTLV-1), is associated with the development of B-cell leukemia. Whereas the natural disease in cattle is characterized by a low tumor incidence, experimental infection of sheep leads to overt leukemia in the majority of infected animals, providing a model for studying the pathogenesis associated with BLV and HTLV-1. Tax(BLV), the major oncoprotein, initiates a cascade of events leading toward malignancy, although the basis of transformation is not fully understood. We have taken a cross-species ovine-to-human microarray approach to identify Tax(BLV)-responsive transcriptional changes in two sets of cultured ovine B cells following retroviral vector-mediated delivery of Tax(BLV). Using cDNA-spotted microarrays comprising 10,336 human genes/expressed sequence tags, we identified a cohort of differentially expressed genes, including genes related to apoptosis, DNA transcription, and repair; proto-oncogenes; cell cycle regulators; transcription factors; small Rho GTPases/GTPase-binding proteins; and previously reported Tax(HTLV-1)-responsive genes. Interestingly, genes known to be associated with human neoplasia, especially B-cell malignancies, were extensively represented. Others were novel or unexpected. The results suggest that Tax(BLV) deregulates a broad network of interrelated pathways rather than a single B-lineage-specific regulatory process. Although cross-species approaches do not permit a comprehensive analysis of gene expression patterns, they can provide initial clues for the functional roles of genes that participate in B-cell transformation and pinpoint molecular targets not identified using other methods in animal models.
Mesh Headings (Keywords): Animals, B-Lymphocytes, Blotting, Northern, Cell Transformation, Viral, Gene Expression Profiling, Gene Expression Regulation, Gene Products, tax, Humans, Leukemia Virus, Bovine, Oligonucleotide Array Sequence Analysis, Reverse Transcriptase Polymerase Chain Reaction, Sheep
Check for Full Text / PubMed Unique Identifier (PMID): 16439548
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