RESUMEN
Wilms' tumors, or nephroblastomas, are thought to arise from abnormal postnatal retention and dysregulated differentiation of nephrogenic progenitor cells that originate as a condensed metanephric mesenchyme within embryonic kidneys. We have previously shown that the transcriptional regulator CITED1 (CBP/p300-interacting transactivators with glutamic acid [E]/aspartic acid [D]-rich C-terminal domain) is expressed exclusively in these nephrogenic progenitor cells and is downregulated as they differentiate to form nephronic epithelia. In the current study, we show that CITED1 expression persists in blastemal cell populations of both experimental rat nephroblastomas and human Wilms' tumors, and that primary human Wilms' tumors presenting with disseminated disease show the highest level of CITED1 expression. Unlike the predominantly cytoplasmic subcellular localization of CITED1 in the normal developing kidney, CITED1 is clearly detectable in the nuclear compartment of Wilms' tumor blastema. These findings indicate that CITED1 is a marker of primitive blastema in Wilms' tumors and suggest that persistent expression and/or altered subcellular localization of CITED1 in the condensed metanephric mesenchyme could play a role in Wilms' tumor initiation and pathogenesis.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias Renales/metabolismo , Riñón/metabolismo , Proteínas Nucleares/metabolismo , Factores de Transcripción/metabolismo , Tumor de Wilms/metabolismo , Animales , Proteínas Reguladoras de la Apoptosis , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Humanos , Riñón/embriología , Riñón/patología , Neoplasias Renales/genética , Neoplasias Renales/patología , Estadificación de Neoplasias , Proteínas Nucleares/análisis , Proteínas Nucleares/genética , ARN Mensajero/análisis , ARN Mensajero/metabolismo , Ratas , Ratas Endogámicas , Transactivadores , Factores de Transcripción/análisis , Factores de Transcripción/genética , Tumor de Wilms/genética , Tumor de Wilms/patologíaRESUMEN
The role of Bordetella bronchiseptica in a natural outbreak of canine infectious respiratory disease was investigated both by culture and serological analysis. B. bronchiseptica was found in the lungs of a large proportion of clinically healthy dogs and in a greater proportion of dogs with respiratory disease. Using a lipopolysaccharide (LPS) antigen-based enzyme-linked immunosorbent assay, we analyzed the serological responses of a large number of dogs. Dogs with high antibody levels showed no protection from disease, and there was no correlation between the development of disease and rising antibody titer. Similarly, there was no difference in antibody levels in dogs with and without B. bronchiseptica in the lungs. Antibodies to LPS have no predictive value in determining which animals will contract respiratory disease, how severe the disease will be, or which dogs will have B. bronchiseptica colonizing the lungs.