在激活蛋白1(activator protein 1,AP-1)二聚体复合物转录因子家族的FOS亚家族成员中,由FOSL1基因编码的转录因子Fra-1对人类肿瘤的转移和进展起到至关重要的作用。Fra-1在大多数肿瘤中表达上调,且被不同的信号通路激活。同时,Fra-1作...在激活蛋白1(activator protein 1,AP-1)二聚体复合物转录因子家族的FOS亚家族成员中,由FOSL1基因编码的转录因子Fra-1对人类肿瘤的转移和进展起到至关重要的作用。Fra-1在大多数肿瘤中表达上调,且被不同的信号通路激活。同时,Fra-1作为重要的转录因子,可以调控多种蛋白的表达,例如上皮间充质转化(epithelial-mesenchymal transition,EMT)相关蛋白基质金属蛋白酶1(matrix metalloproteinases-1,MMP-1)、MMP-9等。在该文中将主要介绍Fra-1在不同肿瘤中发挥的不同作用以及涉及到的不同的信号通路。展开更多
目的检测细胞外调节蛋白激酶(extracellular signal regulated protein kinase,ERK)、(Fos related antigen-1,Fra-1)基因在喉鳞状细胞癌(laryngeal squamous carcinoma cell,LSCC)中表达情况,观察喉癌Hep-2细胞中应用ERK抑制后Fra-1表...目的检测细胞外调节蛋白激酶(extracellular signal regulated protein kinase,ERK)、(Fos related antigen-1,Fra-1)基因在喉鳞状细胞癌(laryngeal squamous carcinoma cell,LSCC)中表达情况,观察喉癌Hep-2细胞中应用ERK抑制后Fra-1表达变化,分析LSCC中Fra-1表达在多个参数组别中的影响。方法采用免疫组化SP法检测47例LSCC和21例癌旁组织中ERK和Fra-1表达情况,逆转录-多聚酶链反应(reverse transcription-polymerase chain reaction,RT-PCR)检测加入ERK抑制剂(SCH772984)实验组与对照组的人喉癌Hep-2细胞中Fra-1 mRNA表达量,分析LSCC中Fra-1基因蛋白表达与各参数的关系。结果 LSCC中ERK、Fra-1蛋白表达均高于癌旁组织ERK(P<0.01),Fra-1(P<0.05),实验组中Fra-1mRNA表达量明显低于对照组(P<0.01)。LSCC中Fra-1蛋白水平表达与临床分期、淋巴结转移、吸烟相关,与病理分级、年龄、解剖分区无关。结论 LSCC中ERK、Fra-1蛋白水平表达均增高,Hep-2细胞中ERK基因受抑制后明显降低Fra-1基因的表达活性。ERK和Fra-1基因之间可能关联表达促进喉癌的发生与发展。展开更多
The tumor microenvironment （TME） plays a prominent role in the growth of tumor cells. As the major inflammatory component of the TME, M2d macrophages are educated by the TME such that they adopt an immunosnppressive...The tumor microenvironment （TME） plays a prominent role in the growth of tumor cells. As the major inflammatory component of the TME, M2d macrophages are educated by the TME such that they adopt an immunosnppressive role that promotes tumor metastasis and progression. Fra-1 forms activator protein-1 heterodimers with Jun partners and drives gene transcription. Fra-1 is thought to drastically induce tumorigenesis and progression. However, the functional role of Fra-1 in the generation of M2d macrophages is poorly understood to date. Here, we demonstrate that 4T1 mammary carcinoma cells, when co-cultured with RAW264.7 macrophage cells, skew the RAW264.7 macrophage cell differentiation into M2d macrophages. The 4T1 cells stimulate de novo overexpression of Fra-1 in RAW264.7 cells, and then Fra-1 binds to the interleukin 6 （IL-6） promoter to increase the production of the cytokine IL-6 in RAW264.7 cells. IL-6 acts in an autocrine fashion to skew RAW264.7 macrophage cell differentiation into M2d macrophages. These findings open new insights into how to reverse M2d macrophage-induced immune tolerance to improve the efficacy of immunotherapeutic approaches.展开更多
文摘在激活蛋白1(activator protein 1,AP-1)二聚体复合物转录因子家族的FOS亚家族成员中,由FOSL1基因编码的转录因子Fra-1对人类肿瘤的转移和进展起到至关重要的作用。Fra-1在大多数肿瘤中表达上调,且被不同的信号通路激活。同时,Fra-1作为重要的转录因子,可以调控多种蛋白的表达,例如上皮间充质转化(epithelial-mesenchymal transition,EMT)相关蛋白基质金属蛋白酶1(matrix metalloproteinases-1,MMP-1)、MMP-9等。在该文中将主要介绍Fra-1在不同肿瘤中发挥的不同作用以及涉及到的不同的信号通路。
文摘The tumor microenvironment （TME） plays a prominent role in the growth of tumor cells. As the major inflammatory component of the TME, M2d macrophages are educated by the TME such that they adopt an immunosnppressive role that promotes tumor metastasis and progression. Fra-1 forms activator protein-1 heterodimers with Jun partners and drives gene transcription. Fra-1 is thought to drastically induce tumorigenesis and progression. However, the functional role of Fra-1 in the generation of M2d macrophages is poorly understood to date. Here, we demonstrate that 4T1 mammary carcinoma cells, when co-cultured with RAW264.7 macrophage cells, skew the RAW264.7 macrophage cell differentiation into M2d macrophages. The 4T1 cells stimulate de novo overexpression of Fra-1 in RAW264.7 cells, and then Fra-1 binds to the interleukin 6 （IL-6） promoter to increase the production of the cytokine IL-6 in RAW264.7 cells. IL-6 acts in an autocrine fashion to skew RAW264.7 macrophage cell differentiation into M2d macrophages. These findings open new insights into how to reverse M2d macrophage-induced immune tolerance to improve the efficacy of immunotherapeutic approaches.
