Zhang Jing, Lodish Harvey F
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts, USA.
Cell Cycle. 2007 Aug 15;6(16):1970-3. doi: 10.4161/cc.6.16.4577. Epub 2007 Jun 10.
K-ras is one of the most frequently mutated genes in virtually all types of human cancers. Using mouse fetal liver erythroid progenitors as a model system, we studied the role of endogenous K-ras signaling in erythroid differentiation. When oncogenic K-ras is expressed from its endogenous promoter, it hyperactivates cytokine-dependent signaling pathways and results in a partial block in erythroid differentiation. In erythroid progenitors deficient in K-ras, cytokine-dependent Akt activation is greatly reduced, leading to delays in erythroid differentiation. Thus, both loss- and gain-of-Kras functions affect erythroid differentiation through modulation of cytokine signaling. These results support the notion that in human cancer patients oncogenic Ras signaling might be controlled by antagonizing essential cytokines.
K-ras是几乎所有类型人类癌症中最常发生突变的基因之一。我们以小鼠胎儿肝脏红系祖细胞作为模型系统，研究了内源性K-ras信号在红系分化中的作用。当致癌性K-ras从其内源启动子表达时，它会过度激活细胞因子依赖性信号通路，并导致红系分化部分受阻。在缺乏K-ras的红系祖细胞中，细胞因子依赖性Akt激活显著降低，导致红系分化延迟。因此，Kras功能的丧失和获得均通过调节细胞因子信号影响红系分化。这些结果支持了这样一种观点，即在人类癌症患者中，致癌性Ras信号可能通过拮抗必需细胞因子来控制。
