JAK-STAT(janus tyrosine kinase-signal transducer and activator of transcription)细胞信号转导途径的紊乱,是肿瘤发生最重要的原因之一.近年来的研究发现,STAT-3作为JAK-STAT信号转导途径中一个重要的调节分子,能够通过将信号直接...JAK-STAT(janus tyrosine kinase-signal transducer and activator of transcription)细胞信号转导途径的紊乱,是肿瘤发生最重要的原因之一.近年来的研究发现,STAT-3作为JAK-STAT信号转导途径中一个重要的调节分子,能够通过将信号直接转导入细胞核而快速激活下游基因,从而保证相应配体顺利完成信号转导过程.然而,STAT-3也有其"黑暗"的一面,其往往在恶性肿瘤细胞中表现为持续活化,作为一种原癌基因,成为肿瘤治疗的新靶标.因而,对近年来有关STAT-3的持续活化与恶性肿瘤细胞的侵袭、转移过程及肿瘤干细胞的关系作一概述,有助于深入了解STAT-3在肿瘤发生发展机制中发挥的作用.展开更多
AIM: To investigate the role of genes and kinetics of specific transcription factors in liver regeneration, and to analyze the gene expression and the activity of some molecules crucially involved in hepatic regenerat...AIM: To investigate the role of genes and kinetics of specific transcription factors in liver regeneration, and to analyze the gene expression and the activity of some molecules crucially involved in hepatic regeneration. METHODS: USING gel-shift assay and RT-PCR, transcription factors, such as NF-κB, STAT-3, SMAD3 and AP-1, and gene expression of inducible nitric oxide synthase (iNOS), hepatocyte growth factor (HGF) and c-met were analyzed in an animal model of chemically induced hepatectomy. RESULTS: Gene expression of HGF and its receptor c-met peaked at 3 h and 24 h after acute CCl4 intoxi- cation. iNOS expression was only observed from 6 to 48 h. Transcriptional factor NF-κB had an early activation at 30 min after acute liver damage. STAT-3 peaked 3 h post- intoxication, while AP-1 displayed a peak of activation at 48 h. SMAD3 showed a high activity at all analyzed times. CONCLUSION: TNF-α and IL-6 play a central role in hepatic regeneration. These two molecules are responsible for triggering the cascade of events and switch-on of genes involved in cell proliferation, such as growth factors, kinases and cyclins which are direct participants of cell proliferation.展开更多
文摘JAK-STAT(janus tyrosine kinase-signal transducer and activator of transcription)细胞信号转导途径的紊乱,是肿瘤发生最重要的原因之一.近年来的研究发现,STAT-3作为JAK-STAT信号转导途径中一个重要的调节分子,能够通过将信号直接转导入细胞核而快速激活下游基因,从而保证相应配体顺利完成信号转导过程.然而,STAT-3也有其"黑暗"的一面,其往往在恶性肿瘤细胞中表现为持续活化,作为一种原癌基因,成为肿瘤治疗的新靶标.因而,对近年来有关STAT-3的持续活化与恶性肿瘤细胞的侵袭、转移过程及肿瘤干细胞的关系作一概述,有助于深入了解STAT-3在肿瘤发生发展机制中发挥的作用.
基金Supported by CONACyT grant # 28827-M to Adriana Salazar-Montes and, in part, by COECyTJal grant # 08-2004 to Juan Armendariz-Borunda
文摘AIM: To investigate the role of genes and kinetics of specific transcription factors in liver regeneration, and to analyze the gene expression and the activity of some molecules crucially involved in hepatic regeneration. METHODS: USING gel-shift assay and RT-PCR, transcription factors, such as NF-κB, STAT-3, SMAD3 and AP-1, and gene expression of inducible nitric oxide synthase (iNOS), hepatocyte growth factor (HGF) and c-met were analyzed in an animal model of chemically induced hepatectomy. RESULTS: Gene expression of HGF and its receptor c-met peaked at 3 h and 24 h after acute CCl4 intoxi- cation. iNOS expression was only observed from 6 to 48 h. Transcriptional factor NF-κB had an early activation at 30 min after acute liver damage. STAT-3 peaked 3 h post- intoxication, while AP-1 displayed a peak of activation at 48 h. SMAD3 showed a high activity at all analyzed times. CONCLUSION: TNF-α and IL-6 play a central role in hepatic regeneration. These two molecules are responsible for triggering the cascade of events and switch-on of genes involved in cell proliferation, such as growth factors, kinases and cyclins which are direct participants of cell proliferation.
