FoxM1 转录因子的多面性：来自转基因小鼠模型的启示。
Multiple faces of FoxM1 transcription factor: lessons from transgenic mouse models.
机构信息
Division of Pulmonary Biology and Perinatal Institute of the Cincinnati Children's Hospital Research Foundation, Cincinnati, OH, USA.
出版信息
Cell Cycle. 2011 Feb 1;10(3):396-405. doi: 10.4161/cc.10.3.14709.
Abstract
FoxM1 transcription factor (previously called HFH-11B, Trident, FoxM1b, Win, and MPP2) is expressed in actively dividing cells and critical for cell cycle progression. FoxM1 expression is induced in a variety of tissues during embryogenesis, and Foxm1 (-/-) mice exhibit embryonic lethal phenotype due to multiple abnormalities in the liver, heart, lung and blood vessels. FoxM1 levels are dramatically decreased in adult tissues, but FoxM1 expression is re-activated during organ injury and numerous cancers. In this review, we discussed the role of FoxM1 in different cell lineages using recent data from transgenic mouse models with conditional "gain-of-function" and "loss-of-function" of FoxM1, as well as tissue samples from human patients. In addition, we provided experimental data showing additional sites of FoxM1 expression in the mouse embryo. Novel cell-autonomous roles of FoxM1 in embryonic development, organ injury and cancer formation in vivo were analyzed. Potential application of these findings for the diagnosis and treatment of human diseases were discussed.
摘要
FoxM1 转录因子（以前称为 HFH-11B、三叉戟、FoxM1b、Win 和 MPP2）在活跃分裂的细胞中表达，对细胞周期进程至关重要。FoxM1 在胚胎发生过程中在多种组织中表达，并且 Foxm1（-/-）小鼠由于肝脏、心脏、肺和血管中的多种异常而表现出胚胎致死表型。FoxM1 水平在成人组织中显著降低，但在器官损伤和多种癌症中 FoxM1 表达被重新激活。在这篇综述中，我们使用来自具有条件“获得功能”和“丧失功能”的 FoxM1 的转基因小鼠模型以及来自人类患者的组织样本的最新数据，讨论了 FoxM1 在不同细胞谱系中的作用。此外，我们提供了实验数据，显示了 FoxM1 在小鼠胚胎中的其他表达部位。分析了 FoxM1 在体内胚胎发育、器官损伤和癌症形成中的新的细胞自主作用。讨论了这些发现对人类疾病诊断和治疗的潜在应用。
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