title: Insights into gene expression changes impacting B-cell transformation: cross-species microarray analysis of bovine leukemia virus tax-responsive genes in ovine B cells.
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.
authors.affiliation: Laboratory of Experimental Hematology, Bordet Institute, 121 Blvd. de Waterloo, 1000 Brussels, Belgium.
authors.forename: Pavel
authors.initials: P
authors.lastname: Klener
authors.forename: Maud
authors.initials: M
authors.lastname: Szynal
authors.forename: Yvette
authors.initials: Y
authors.lastname: Cleuter
authors.forename: Makram
authors.initials: M
authors.lastname: Merimi
authors.forename: Hugues
authors.initials: H
authors.lastname: Duvillier
authors.forename: Françoise
authors.initials: F
authors.lastname: Lallemand
authors.forename: Claude
authors.initials: C
authors.lastname: Bagnis
authors.forename: Philip
authors.initials: P
authors.lastname: Griebel
authors.forename: Christos
authors.initials: C
authors.lastname: Sotiriou
authors.forename: Arsène
authors.initials: A
authors.lastname: Burny
authors.forename: Philippe
authors.initials: P
authors.lastname: Martiat
authors.forename: Anne
authors.initials: A
authors.lastname: Van den Broeke
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology* / Q000821:virology*; D015152:Blotting, Northern; D002472:Cell Transformation, Viral / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016356:Gene Products, tax / Q000502:physiology*; D006801:Humans; D001909:Leukemia Virus, Bovine / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep
chemical_list: D016356:Gene Products, tax