RESUMEN
The product of Snail gene is a repressor of E-cadherin transcription and an inductor of the epithelial-to-mesenchymal transition in several epithelial tumor cell lines. In order to examine Snail expression in animal and human tissues, we have raised a monoclonal antibody (MAb) that reacts with the regulatory domain of this protein. Analysis of murine embryos shows that Snail is expressed in extraembryonic tissues and embryonic mesoderm, in mesenchymal cells of lungs and dermis as well as in cartilage. Little reactivity was detected in adult tissues as Snail was not constitutively expressed in most mesenchymal cells. However, Snail expression was observed in activated fibroblasts involved in wound healing in mice skin. Moreover, Snail was detected in pathological conditions causing hyperstimulation of fibroblasts, such as fibromatosis. Analysis of Snail expression in tumors revealed that it was highly expressed in sarcomas and fibrosarcomas. In epithelial tumors, it presented a more limited distribution, restricted to stromal cells placed in the vicinity of the tumor and to tumoral cells in the same areas. These results demonstrate that Snail is present in activated mesenchymal cells, indicate its relevance in the communication between tumor and stroma and suggest that it can promote the conversion of carcinoma cells to stromal cells.
Asunto(s)
Células del Estroma/fisiología , Factores de Transcripción/genética , Células 3T3 , Animales , Línea Celular Tumoral , Neoplasias del Colon , Embrión de Mamíferos , Femenino , Regulación del Desarrollo de la Expresión Génica , Humanos , Ratones , Embarazo , ARN Neoplásico/genética , Proteínas Recombinantes de Fusión/farmacología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Transcripción de la Familia Snail , Células del Estroma/patología , Factores de Transcripción/fisiología , Cicatrización de Heridas/genética , Cicatrización de Heridas/fisiologíaRESUMEN
The A1555G mutation of the mtDNA is associated with both aminoglycoside-induced and non-syndromic hearing loss. The A1555G is relatively frequent in the Spanish and some Asian populations, but has only been reported rarely in other populations, possibly because of ascertainment bias. We studied 85 Danish patients with varying degrees of hearing impairment and found two patients with the A1555G mutation (2.4%). Neither had received aminoglycosides. Our study indicates that the mutation might not be uncommon in Danish patients with hearing impairment.
