RESUMO
In this paper, patterns of allelic imbalances (Als) in chemically induced rat mammary, colon, and bladder tumors from (Wistar Furth x Fischer 344)F1 rats are described and compared. Male F1 rats were administered azoxymethane (AOM), and colon tumors were collected at 58 wk after treatment. Female F1 rats were given either N-nitroso-N-methylurea (NMU) or N-butyl-(hydroxybutyl)-nitrosoamine (BBN), and mammary and bladder tumors were collected at 15 and 52 wk after treatment, respectively. DNA was extracted from a subset of 18 of the largest tumors from each group, and a genome scan was performed by using polymerase chain reaction and 90 polymorphic microsatellite markers. Als, such as loss of heterozygosity, gene duplication, and microsatellite instability, were observed at low frequencies in all of the tumor models. Thirty random Als were observed in the AOM-induced colon tumors but only four in the NMU-induced mammary tumors. In both these models, all the tumors were classified as adenocarcinomas, and most of the Als observed were confined to single tumors with atypical histopathology. In contrast, 27 random Als were identified in the BBN-induced bladder tumors. Als were observed in both transitional-cell carcinomas and papillomas, although most were in the carcinomas. Statistical analysis of the Al data revealed no significant nonrandom Als within or among the tumor models, although several of the infrequently observed Al events identified in the rat tumors may also be observed in the corresponding human tumor type.
Assuntos
Carcinógenos/toxicidade , Mapeamento Cromossômico , Neoplasias do Colo/genética , Perda de Heterozigosidade , Neoplasias Mamárias Experimentais/genética , Repetições de Microssatélites , Mutação Puntual , Neoplasias da Bexiga Urinária/genética , Alelos , Animais , Azoximetano/toxicidade , Butilidroxibutilnitrosamina/toxicidade , Códon , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/patologia , Feminino , Genes ras , Marcadores Genéticos , Humanos , Masculino , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/patologia , Metilnitrosoureia/toxicidade , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos WF , Neoplasias da Bexiga Urinária/induzido quimicamente , Neoplasias da Bexiga Urinária/patologiaRESUMO
The expression of rat 24p3, encoded by the Lcn2 gene, has been associated with rat mammary carcinomas initiated by the neu oncogene (Stoesz and Gould, 1995). In this study, we assign the Lcn2 gene to rat chromosome band 3q12 by genetic linkage analysis.
Assuntos
Proteínas de Fase Aguda/genética , Mapeamento Cromossômico , Proteínas Oncogênicas/genética , Animais , Cromossomos Humanos Par 9/genética , Cruzamentos Genéticos , Humanos , Lipocalina-2 , Lipocalinas , Escore Lod , Camundongos , Repetições de Microssatélites/genética , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas , Ratos , Ratos Endogâmicos , Homologia de Sequência do Ácido NucleicoRESUMO
Fifty-five novel rat microsatellite markers were isolated from libraries specific for rat chromosomes (Chrs) 1, 2, and 7. The markers were mapped in three backcross rat populations. Thirty of these markers mapped to Chrs 1, 2, or 7, while the other 25 mapped to other chromosomes. New markers for two genes, liver-specific transporter gene (Livtr) and insulin-responsive glucose transporter (Glut4), were also mapped to rat Chrs 9 and 10, respectively. Three provisionally assigned markers from previous studies were also confirmed. Detailed methodologies for the generation and enrichment of clones containing repeat sequences and for the isolation of chromosome-specific markers are presented, since they represent unique combinations and modifications of previous protocols. Such methods and the newly presented markers should be useful for both specific and general mapping studies in the rat.
Assuntos
Mapeamento Cromossômico , Biblioteca Gênica , Repetições de Microssatélites , Proteínas Musculares , Ratos Endogâmicos/genética , Animais , Sequência de Bases , Proteínas de Transporte/genética , Cruzamentos Genéticos , Feminino , Ligação Genética , Marcadores Genéticos , Transportador de Glucose Tipo 4 , Fígado/metabolismo , Masculino , Dados de Sequência Molecular , Proteínas de Transporte de Monossacarídeos/genética , Reação em Cadeia da Polimerase , Ratos , Ratos Endogâmicos F344/genética , Ratos Endogâmicos WF/genética , Ratos Endogâmicos WKY/genéticaRESUMO
We have used a rat model of induced mammary carcinomas in an effort to identify breast cancer susceptibility genes. Using genetic crosses between the carcinoma-resistant Copenhagen (COP) and carcinoma-sensitive Wistar-Furth rats, we have confirmed the identification of the Mcs1 locus that modulates tumor number. We have now also identified two additional loci, Mcs2 and Mcs3. These three loci map to chromosomes 2, 7, and 1, respectively, and interact additively to suppress mammary carcinoma development in the COP strain. They are responsible for a major portion of the tumor-resistant phenotype of the COP rat. No loss of heterozygosity was observed surrounding the three loci. A fourth COP locus, Mcs4, has also been identified on chromosome 8 and acts in contrast to increase the number of carcinomas. These results show that mammary carcinoma susceptibility in the COP rat is a polygenic trait. Interestingly, a polymorphism in the human genomic region homologous to the rat Mcs4 region is associated with an increased breast cancer risk in African-American women. The isolation of the Mcs genes may help elucidate novel mechanisms of carcinogenesis, provide information important for human breast cancer risk estimation, and also provide unique drug discovery targets for breast cancer prevention.
Assuntos
Neoplasias Mamárias Animais/genética , Alelos , Animais , Cruzamentos Genéticos , Modelos Animais de Doenças , Feminino , Dosagem de Genes , Ligação Genética , Marcadores Genéticos , Predisposição Genética para Doença , Perda de Heterozigosidade , Ratos , Ratos Endogâmicos WFRESUMO
We have mapped 11 novel, anonymous genetic markers to rat chromosome 2. The rat ceruloplasmin gene (Cp) had been previously mapped to chromosomes 2 and 7q11-->q13 by two different methods. To resolve the assignment and to localize the Cp gene on the rat genetic linkage map, we used linkage analysis to confirm that rat Cp lies on chromosome 2.
