title: Molecular analysis of the fragile histidine triad (FHIT) tumor suppressor gene in vesical tumors of cattle with chronic enzootic hematuria (CEH).
abstract: The FHIT (fragile histidine triad) gene is a tumor suppressor gene known to be inactivated in many tumors including bladder tumors and is spanning FRA3B, a very active common fragile site in the human genome. We have recently isolated the bovine gene, and the aim of this study was to test whether FHIT presents altered expression patterns in vesical tumors of cattle with CEH (chronic enzootic hematuria). CEH is a common syndrome affecting Mediterranean cattle: clastogenic, mutagenic and cancerogenic substances released by the bracken fern (Pteridium spp) grazed by animals induce the formation of neoplastic lesions, among which bladder tumors have a high incidence. We analysed FHIT in 23 bladder tumors of CEH cattle looking at: 1) the methylation status of the CpG island comprising the promoter and part of exon 1; 2) the presence of altered FHIT transcripts; 3) the mRNA expression levels measured with a quantitative real time PCR (QRT-PCR) approach. Our results suggest that unlike in human tumors, FHIT in vesical tumors of CEH cattle is largely unmethylated. Furthermore, the same mRNA isoforms of FHIT were detected in tumors and in healthy tissues, including a novel isoform that was found in this study. Finally, QRT-PCR data did not reveal significantly altered expression profiles of FHIT transcripts. Further studies and larger sets of cases will be useful to confirm this finding, but the data seem to suggest that epigenetic modifications of FHIT and altered expression profiles are not a hallmark of bovine vesical tumors like they are in human tumors.
authors.affiliation: Department of Genetics and Microbiology A. Buzzati-Traverso, University of Pavia, Pavia, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Guidi
authors.forename: C
authors.initials: C
authors.lastname: Uboldi
authors.forename: L
authors.initials: L
authors.lastname: Ferretti
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D052688:Bovine papillomavirus 1 / Q000302:isolation & purification / Q000472:pathogenicity; D002417:Cattle; D002418:Cattle Diseases / Q000209:etiology / Q000235:genetics*; D043283:Chromosome Fragile Sites / Q000235:genetics; D002908:Chronic Disease; D019175:DNA Methylation; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D006417:Hematuria / Q000209:etiology / Q000235:genetics / Q000662:veterinary*; D009363:Neoplasm Proteins / Q000235:genetics*; D030361:Papillomavirus Infections / Q000235:genetics / Q000662:veterinary; D010939:Plant Poisoning / Q000235:genetics / Q000662:veterinary; D032498:Pteridium / Q000506:poisoning; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D013577:Syndrome; D001749:Urinary Bladder Neoplasms / Q000209:etiology / Q000235:genetics / Q000662:veterinary*; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000099170:Bis(5'-adenosyl)triphosphatase