Scholl Florence A, Dumesic Phillip A, Khavari Paul A
VA Palo Alto Healthcare System, Palo Alto, CA, USA; Program in Epithelial Biology, Standford University School of Medicine, Stanford, CA, USA.
Cancer Lett. 2005 Dec 8;230(1):1-5. doi: 10.1016/j.canlet.2004.12.013. Epub 2005 Jan 18.
Cell transformation is often a result of constitutive activation of genes in signaling pathways that regulate cell proliferation and differentiation. Indeed, the Ras/Raf/MEK/ERK mitogen-activated protein kinase (MAPK) signaling pathway is constitutively activated in a large number of cancers. The extent to which a single-gene mutation can alter cell fate, however, remains questionable. In vitro studies have addressed this issue, but organs are comprised of multiple cell types, and in vitro models often poorly approximate these interactions. In response to these limitations, cell-type specific mouse models have been generated as a means to examine the effect of altering a single element of the MAPK pathway in vivo. This review summarizes data from transgenic murine and human tissue models expressing constitutive active forms of MEK1.
细胞转化通常是调节细胞增殖和分化的信号通路中基因组成性激活的结果。事实上,Ras/Raf/MEK/ERK丝裂原活化蛋白激酶(MAPK)信号通路在大量癌症中被组成性激活。然而,单基因突变能在多大程度上改变细胞命运仍存在疑问。体外研究已经探讨了这个问题,但器官由多种细胞类型组成,体外模型往往很难模拟这些相互作用。针对这些局限性,已经构建了细胞类型特异性小鼠模型,作为在体内研究改变MAPK通路单个元件的作用的一种手段。本综述总结了来自表达组成型活性MEK1的转基因小鼠和人类组织模型的数据。