在口腔、食管和结直肠癌病灶中,TATA序列结合蛋白相关因子1(TATA-box binding protein associated factor 1 like,TAF1L)、stomatin家族蛋白1(stomatin-like protein 1,STOML1)和stomatin家族蛋白2(stomatin-like protein 2,STOML2)存...在口腔、食管和结直肠癌病灶中,TATA序列结合蛋白相关因子1(TATA-box binding protein associated factor 1 like,TAF1L)、stomatin家族蛋白1(stomatin-like protein 1,STOML1)和stomatin家族蛋白2(stomatin-like protein 2,STOML2)存在异常表达.为探究它们在消化系统癌变过程中的作用机理,利用6种消化道肿瘤(食道、胃、结肠、直肠、肝脏和胰腺)及癌旁组织的微陈列芯片,通过多重免疫组织化学染色,比对分析TAF1L、STOML1和STOML2这3种蛋白质在癌与癌旁组织的差异表达及与癌变的关联.结果发现,STOML2在食道、胃、结肠、直肠、肝脏和胰腺这6种消化系统癌组织中均呈显著性高表达(P<0.001),而同一家族成员STOML1则仅在食管癌和肝癌组织中表达明显增高(P<0.005).另外,除胰腺癌灶外,TAF1L在其余5种消化系统癌组织中也呈现高表达(P<0.005).同时,TAF1L、STOML1和STOML2这3种蛋白质均与上皮间充质转化的关键蛋白质MMP9有共定位现象.由此表明,3种蛋白质TAF1L、STOML1和STOML2在多种癌组织中可能具有广泛的促癌作用.由于3种蛋白质在多种癌组织的表达水平不同,说明它们各自存在着组织特异性,且具有不同的功能使命,需进一步研究TAF1L、STOML1和STOML2这3种蛋白质在消化系统恶性肿瘤发生发展过程中各自的分子病理学潜能,如能将它们打造成用于精准诊疗和预后判断的新型分子标志物,此研究结果将有重要的临床意义.展开更多
The GATA family consists of six members, GATA 1-6. In this study, we focused on GATA-2, which is expressed predominantly in hematopoietic progenitor cells and plays the key role in keeping these cells in the undiffere...The GATA family consists of six members, GATA 1-6. In this study, we focused on GATA-2, which is expressed predominantly in hematopoietic progenitor cells and plays the key role in keeping these cells in the undifferentiated status. CREB-binding proteins (CBP) are essential transcriptional coacti- vators for a large number of regulated DNA-binding transcription factors, including GATA-1. But there have been no reports on whether CBP is still a co-activator of GATA-2. Here, we used the immunopre- cipitation and pull-down experiments to show that the GATA-2 and CBP were physically binding to- gether, and clarified the binding sites CH1, CH3 , CH452 and CT1430 in CBP and N-finger, C-finger and N-C-finger in GATA-2. Luciferase assay results in our experiment indicated that CBP could increase GATA-2 transcriptional activity in the dose-dependent manner. GATA-1 is mainly expressed in differen- tiated hematopoietic cells, but still has overlap expression with GATA-2. CBP is a coactivator of GATA-2 and GATA-1. The investigation on the mechanism that could decide whether CBP binds to GATA-2 to keep hematopoietic cells in the progenitor status or to GATA-1 to start differentiation will be a very in- teresting and very meaningful project in the near future.展开更多
文摘在口腔、食管和结直肠癌病灶中,TATA序列结合蛋白相关因子1(TATA-box binding protein associated factor 1 like,TAF1L)、stomatin家族蛋白1(stomatin-like protein 1,STOML1)和stomatin家族蛋白2(stomatin-like protein 2,STOML2)存在异常表达.为探究它们在消化系统癌变过程中的作用机理,利用6种消化道肿瘤(食道、胃、结肠、直肠、肝脏和胰腺)及癌旁组织的微陈列芯片,通过多重免疫组织化学染色,比对分析TAF1L、STOML1和STOML2这3种蛋白质在癌与癌旁组织的差异表达及与癌变的关联.结果发现,STOML2在食道、胃、结肠、直肠、肝脏和胰腺这6种消化系统癌组织中均呈显著性高表达(P<0.001),而同一家族成员STOML1则仅在食管癌和肝癌组织中表达明显增高(P<0.005).另外,除胰腺癌灶外,TAF1L在其余5种消化系统癌组织中也呈现高表达(P<0.005).同时,TAF1L、STOML1和STOML2这3种蛋白质均与上皮间充质转化的关键蛋白质MMP9有共定位现象.由此表明,3种蛋白质TAF1L、STOML1和STOML2在多种癌组织中可能具有广泛的促癌作用.由于3种蛋白质在多种癌组织的表达水平不同,说明它们各自存在着组织特异性,且具有不同的功能使命,需进一步研究TAF1L、STOML1和STOML2这3种蛋白质在消化系统恶性肿瘤发生发展过程中各自的分子病理学潜能,如能将它们打造成用于精准诊疗和预后判断的新型分子标志物,此研究结果将有重要的临床意义.
基金Supported by the Sci-tech Program of Shandong Provincial Education Department (Grant No. J06N02)
文摘The GATA family consists of six members, GATA 1-6. In this study, we focused on GATA-2, which is expressed predominantly in hematopoietic progenitor cells and plays the key role in keeping these cells in the undifferentiated status. CREB-binding proteins (CBP) are essential transcriptional coacti- vators for a large number of regulated DNA-binding transcription factors, including GATA-1. But there have been no reports on whether CBP is still a co-activator of GATA-2. Here, we used the immunopre- cipitation and pull-down experiments to show that the GATA-2 and CBP were physically binding to- gether, and clarified the binding sites CH1, CH3 , CH452 and CT1430 in CBP and N-finger, C-finger and N-C-finger in GATA-2. Luciferase assay results in our experiment indicated that CBP could increase GATA-2 transcriptional activity in the dose-dependent manner. GATA-1 is mainly expressed in differen- tiated hematopoietic cells, but still has overlap expression with GATA-2. CBP is a coactivator of GATA-2 and GATA-1. The investigation on the mechanism that could decide whether CBP binds to GATA-2 to keep hematopoietic cells in the progenitor status or to GATA-1 to start differentiation will be a very in- teresting and very meaningful project in the near future.
