The Canine RAGE - HMGB1 Complex, a Hand on Metastasis?
Tufts' Canine and Feline Breeding and Genetics Conference, 2005
H Murua Escobar1, JT Soller1,2, KA Sterenczak2, JD Sperveslage2, C.Schlüter2, N Eberle1, S Winkler1,2, J Bullerdiek2 , I Nolte1
1Small Animal Clinic, University of Veterinary Medicine, Germany; 2Centre for Human Genetics, University of Bremen, Germany

Objectives: Primary objective was to characterise the canine receptor for advanced glycation end products (RAGE) gene. The RAGE receptor is a multiligand member of the immunoglobulin superfamily of cell surface molecules known to be causally involved in a variety of pathophysiological processes, e.g. immune/inflammatory disorders, Alzheimer disease, and tumorigenesis. Recently, the RAGE receptor was described to bind a number of ligands with diverse structural features. One of these ligands is amphoterin, synonymously called HMGB1. The RAGE - HMGB1 complex has been shown to have significant influence on inflammation and metastasis by taking significant effect at invasiveness, growth and motility of tumour cells. In vitro and in vivo approaches showed that blocking of this complex resulted in drastic suppression of tumour cell growth. Recently we characterised the canine HMGB1 gene and protein completely.

Results: Here we present the complete characterisation of the canine RAGE gene including its 1384 bp mRNA, the 1215 bp protein coding sequence (cds), the 2835 bp genomic structure, the chromosomal localisation on CFA 12, the gene expression pattern in healthy tissues, and its 404 amino acid protein with a weight of 43113.19 Daltons. Further on we compared the cds of six different canine breeds for SNPs.

Conclusions: The complete characterisation of the canine RAGE-HMGB1 protein complex could serve as base for future clinical studies aimed at the development of blocking strategies to inhibit metastatic behaviour of canine and human tumours.

Speaker Information
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H Murua Escobar
Small Animal Clinic, University of Veterinary Medicine

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