Insights into gene expression changes impacting B-cell transformation: cross-species microarray analysis of bovine leukemia virus tax-responsive genes in ovine B cells.
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.
Klener
Pavel
P
Laboratory of Experimental Hematology, Bordet Institute, 121 Blvd. de Waterloo, 1000 Brussels, Belgium.
Szynal
Maud
M
Cleuter
Yvette
Y
Merimi
Makram
M
Duvillier
Hugues
H
Lallemand
Françoise
F
Bagnis
Claude
C
Griebel
Philip
P
Sotiriou
Christos
C
Burny
Arsène
A
Martiat
Philippe
P
Van den Broeke
Anne
A
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
D016356:Gene Products, tax