Transcriptional changes induced by bovine papillomavirus type 1 in equine fibroblasts.
Bovine papillomavirus type 1 (BPV-1) and, less commonly, BPV-2 are associated with the pathogenesis of common equine skin tumors termed sarcoids. In an attempt to understand the mechanisms by which BPV-1 induces sarcoids, we used gene expression profiling as a screening tool to identify candidate genes implicated in disease pathogenesis. Gene expression profiles of equine fibroblasts transformed by BPV-1 experimentally or from explanted tumors were compared with those of control equine fibroblasts to identify genes associated with expression of BPV-1. Analysis of the microarray data identified 81 probe sets that were significantly (P < 0.01) differentially expressed between the BPV-1-transformed and control cell lines. Expression of several deregulated genes, including MMP-1, CXCL5, FRA-1, NKG7, TLR4, and the gene encoding the major histocompatibility complex class I (MHC-I) protein, was confirmed using other BPV-1-transformed cell lines. Furthermore, expression of these genes was examined using a panel of 10 sarcoids. Increased expression of MMP-1, CXCL5, FRA-1, and NKG7 was detected in a subset of tumors, and TLR4 and MHC I showed robust down-regulation in all tumors. Deregulated expression was confirmed at the protein level for MMP-1 and MHC-I. The present report identifies genes modulated by BPV-1 transformation and will help identify the molecular mechanisms involved in disease pathogenesis.
Yuan
Z Q
ZQ
Institute of Comparative Medicine, University of Glasgow, Faculty of Veterinary Medicine, Bearsden Road, Glasgow G61 1QH, Scotland, United Kingdom.
Nicolson
L
L
Marchetti
B
B
Gault
E A
EA
Campo
M S
MS
Nasir
L
L
D000818:Animals; D052688:Bovine papillomavirus 1; D002461:Cell Line, Transformed; D017931:DNA Primers / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism* / Q000821:virology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006734:Horse Diseases / Q000821:virology*; D006736:Horses; D008285:Major Histocompatibility Complex / Q000235:genetics; D008856:Microscopy, Fluorescence; D020411:Oligonucleotide Array Sequence Analysis; D030361:Papillomavirus Infections / Q000378:metabolism* / Q000821:virology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers