Chang F, Lee J T, Navolanic P M, Steelman L S, Shelton J G, Blalock W L, Franklin R A, McCubrey J A
Department of Microbiology & Immunology, Brody School of Medicine at East Carolina University, Greenville 27858, USA.
Leukemia. 2003 Mar;17(3):590-603. doi: 10.1038/sj.leu.2402824.
The PI3K/Akt signal transduction cascade has been investigated extensively for its roles in oncogenic transformation. Initial studies implicated both PI3K and Akt in prevention of apoptosis. However, more recent evidence has also associated this pathway with regulation of cell cycle progression. Uncovering the signaling network spanning from extracellular environment to the nucleus should illuminate biochemical events contributing to malignant transformation. Here, we discuss PI3K/Akt-mediated signal transduction including its mechanisms of activation, signal transducing molecules, and effects on gene expression that contribute to tumorigenesis. Effects of PI3K/Akt signaling on important proteins controlling cellular proliferation are emphasized. These targets include cyclins, cyclin-dependent kinases, and cyclin-dependent kinase inhibitors. Furthermore, strategies used to inhibit the PI3K/Akt pathway are presented. The potential for cancer treatment with agents inhibiting this pathway is also addressed.
PI3K/Akt信号转导级联因其在致癌转化中的作用而受到广泛研究。最初的研究表明PI3K和Akt都参与了细胞凋亡的预防。然而，最近的证据也将该信号通路与细胞周期进程的调控联系起来。揭示从细胞外环境到细胞核的信号网络，应该能够阐明促成恶性转化的生化事件。在此，我们讨论PI3K/Akt介导的信号转导，包括其激活机制、信号转导分子以及对基因表达的影响，这些影响有助于肿瘤发生。重点强调了PI3K/Akt信号对控制细胞增殖的重要蛋白质的作用。这些靶点包括细胞周期蛋白、细胞周期蛋白依赖性激酶和细胞周期蛋白依赖性激酶抑制剂。此外，还介绍了用于抑制PI3K/Akt信号通路的策略。同时也探讨了使用抑制该信号通路的药物进行癌症治疗的潜力。
