RESUMEN
Down-regulation of E-cadherin expression is a determinant of tumor cell invasiveness, an event frequently associated with epithelial-mesenchymal transitions. Here we show that the mouse E12/E47 basic helix-loop-helix transcription factor (the E2A gene product) acts as a repressor of E-cadherin expression and triggers epithelial-mesenchymal transitions. The mouse E47 factor was isolated in a one-hybrid system designed to isolate repressors of the mouse E-cadherin promoter. Epithelial cells ectopically expressing E47 adopt a fibroblastic phenotype and acquire tumorigenic and migratory/invasive properties, concomitant with the suppression of E-cadherin expression. Suppression of E-cadherin expression under stable or inducible expression of E47 in epithelial cells occurs at the transcriptional level and is dependent on the E-boxes of the E-cadherin promoter. Interestingly, analysis of endogenous E2A expression in murine and human cell lines illustrated its presence in E-cadherin-deficient, invasive carcinoma cells but its absence from epithelial cell lines. This expression pattern is consistent with that observed in early mouse embryos, where E2A mRNA is absent from epithelia but strongly expressed in the mesoderm. These results implicate E12/E47 as a repressor of E-cadherin expression during both development and tumor progression and indicate its involvement in the acquisition and/or maintenance of the mesenchymal phenotype.
Asunto(s)
Cadherinas/genética , Proteínas de Unión al ADN/fisiología , Regulación hacia Abajo/fisiología , Factores de Transcripción , Animales , Secuencia de Bases , Cadherinas/metabolismo , Línea Celular , Cartilla de ADN , Proteínas de Unión al ADN/metabolismo , Perros , Epitelio/metabolismo , Mesodermo/metabolismo , Ratones , Datos de Secuencia Molecular , Unión Proteica , Proteínas Recombinantes/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Transcripción TCF , Proteína 1 Similar al Factor de Transcripción 7Asunto(s)
Bovinos/fisiología , Fenómenos Electromagnéticos/métodos , Lactancia , Glándulas Mamarias Animales/irrigación sanguínea , Reología/veterinaria , Aminoácidos Esenciales/metabolismo , Animales , Bovinos/metabolismo , Femenino , Glucosa/metabolismo , Lactosa/metabolismo , Glándulas Mamarias Animales/metabolismo , Embarazo , Proteínas/metabolismo , Reología/métodos , Triglicéridos/metabolismoRESUMEN
The effect of intramammary infusion of Escherichia coli endotoxin upon mammary blood flow was studied in lactating goats and cows. Blood flow was recorded by means of an electromagnetic flow probe chronically implanted around one mammary artery. Endotoxin mastatis was always accompanied by a significant increase in mammary blood flow, characterized by 2 conspicuous peaks. The flow returned to control values by the thirteenth hour after infusion. Other symptoms of acute mastitis were: fever, increased heart rate, swelling, heat and pain of the gland, increased chloride and total cell count in milk.
Asunto(s)
Endotoxinas/toxicidad , Escherichia coli , Cabras , Glándulas Mamarias Animales/irrigación sanguínea , Mastitis Bovina/fisiopatología , Mastitis/veterinaria , Animales , Velocidad del Flujo Sanguíneo , Bovinos , Cloruros/análisis , Femenino , Mastitis/inducido químicamente , Mastitis/fisiopatología , Mastitis Bovina/inducido químicamente , Leche/análisis , Leche/citología , EmbarazoRESUMEN
The influence of prostaglandins (PG) F2alpha and E2 on milk ejection, mammary artery blood flow and arterial blood pressure was studied in lactating cows. Injections of both PG in the jugular vein or the carotid artery induced milk ejection after a relatively long latency period. The minimal effective dose amounted to 1 to 5 microng and to 100 to 300 microng for PGF2alpha and PGE2 respectively. In several cases with PGF2alpha and once with PGE2 milk ejection was accompanied with a simultaneous increase in blood flow through the mammary artery whereas arterial blood pressure remained unchanged. Both routes of administration showed the same response. It was suggested that the effect of the PG on the bovine myoepithelium is indirect, possibly secondary to a release of oxytocin from the neurohypophysis.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Lactancia/efectos de los fármacos , Arterias Mamarias , Eyección Láctea/efectos de los fármacos , Prostaglandinas E/farmacología , Prostaglandinas F/farmacología , Flujo Sanguíneo Regional/efectos de los fármacos , Arterias Torácicas , Animales , Bovinos , Femenino , Inyecciones Intraarteriales , Inyecciones Intravenosas , Embarazo , Prostaglandinas E/administración & dosificación , Prostaglandinas F/administración & dosificación , Factores de TiempoRESUMEN
Injections of prostaglandins F2alpha (threshold dose: 1 to 5 microgram) and E2 (threshold dose: 1000 to 300 microgram) in the jugular vein or the carotid artery induced milk ejection in lactating cows after a relatively long latency period. In several cases with PGF2alpha and in one case with PGE2, milk ejection was accompanied by a simultaneous increase in blood flow through the mammary artery. Both routes of administration showed the same response. It is suggested that the effect of the prostaglandins on milk ejection is indirect, possibly secondary to a release of oxytocin from the neurohypophysis.