RESUMEN
The transcription factor STAT5 is constitutively tyrosine phosphorylated and activated after transformation of hematopoietic cells by p210Bcr/Abl. A truncated form of STAT5B (triangle upSTAT5; aa, 1-683) that lacks tyrosine 699 and the transcriptional activation domain was introduced into Ba/F3p210 cells under the control of a tetracycline-inducible promoter. Treatment of these cells with doxycycline, a tetracycline analogue, induced expression of triangle upSTAT5 and inhibited STAT5-dependent transcription. triangle upSTAT5 coprecipitated with STAT5 and decreased Bcr/Abl-dependent tyrosine phosphorylation of endogenous STAT5. Induction of triangle upSTAT5 inhibited growth of Ba/F3p210 cells (26%-52% of control levels at 4 days) but did not cause cell-cycle arrest. triangle upSTAT5 reduced viability of Ba/F3p210 cells and increased sensitivity of the cells to the cytotoxic drugs hydroxyurea and cytarabine. These results indicate that high-level expression of triangle upSTAT5, as achieved here by using a tetracycline-inducible promoter, inhibits STAT5 activity, reduces the growth rate of Ba/F3p210 cells by inhibiting viability, and results in increased sensitivity to chemotherapeutic drugs. It is therefore likely that STAT5 activation plays a role in the transformation of hematopoietic cell lines by p210Bcr/Abl. (Blood. 2000;95:2118-2125)
Asunto(s)
Proteínas de Unión al ADN/metabolismo , Proteínas de Fusión bcr-abl/metabolismo , Proteínas de la Leche , Transactivadores/metabolismo , Animales , Antibacterianos/farmacología , Antimetabolitos Antineoplásicos/farmacología , Ciclo Celular , División Celular , Línea Celular , Línea Celular Transformada , Supervivencia Celular , Citarabina/farmacología , ADN Complementario/metabolismo , Proteínas de Unión al ADN/fisiología , Relación Dosis-Respuesta a Droga , Doxiciclina/farmacología , Inhibidores Enzimáticos/farmacología , Genes Reporteros , Hidroxiurea/farmacología , Ratones , Mutación , Fosforilación , Regiones Promotoras Genéticas , Factor de Transcripción STAT5 , Factores de Tiempo , Transactivadores/fisiología , Tirosina/metabolismoRESUMEN
Chickens 14 days old were experimentally inoculated with Mycoplasma gallisepticum (MG) R-P10 strain. After development of respiratory symptoms, birds were left unmedicated or medicated for 5 consecutive days with Difloxacin 5, 7.5 or 10 mg/kg body weight per day or Enrofloxacin at the dose level of 10 mg/kg body weight per day. Evaluation of efficacy was based on body weight, symptoms, post-mortem findings, re-isolation of MG and serology. Results indicated that under the conditions of this experiment, treatment with 7.5 mg Difloxacin per kg body weight for 5 days was already effective against pathogenic MG infection. The dose of 10 mg/kg Difloxacin was equally effective as a dose of 10 mg/kg Enrofloxacin in treating respiratory symptoms.