The PTEN/PI3K/AKT Pathway in vivo, Cancer Mouse Models.
The PTEN/PI3K/AKT Pathway in vivo, Cancer Mouse Models.
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DOI：
10.3389/fonc.2014.00252
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发表时间：
2014
影响因子：
4.7
通讯作者：
Paramio JM
中科院分区：
文献类型：
--
作者：
Carnero A;Paramio JM
当PI3K（磷脂酰肌醇-3激酶）被受体酪氨酸激酶激活时，它磷酸化PIP2生成PIP3并激活信号通路。10号染色体上缺失的磷酸酶和紧张素同源物使PIP3去磷酸化为PIP2，从而负向调控该通路。AKT （v-akt小鼠胸腺瘤病毒癌基因同源物；蛋白激酶B）在PIP3下游被激活并介导生理过程。此外，在PI3K通路的所有水平上，与其他信号网络存在大量的串扰。由于其多样化的排列、基因突变和扩增，以及其在几种信号转导途径中的核心作用，pi3k依赖轴在许多肿瘤中经常被激活，是一个有吸引力的治疗靶点。这些新疗法的临床前测试和分析需要适当和精心定制的系统。这一途径经过基因修饰的小鼠模型对于理解这一途径在肿瘤发生过程中所起的作用至关重要。在这里，我们回顾了PI3K/AKT通路被基因修饰的癌症小鼠模型。
When PI3K (phosphatidylinositol-3 kinase) is activated by receptor tyrosine kinases, it phosphorylates PIP2 to generate PIP3 and activates the signaling pathway. Phosphatase and tensin homolog deleted on chromosome 10 dephosphorylates PIP3 to PIP2, and thus, negatively regulates the pathway. AKT (v-akt murine thymoma viral oncogene homolog; protein kinase B) is activated downstream of PIP3 and mediates physiological processes. Furthermore, substantial crosstalk exists with other signaling networks at all levels of the PI3K pathway. Because of its diverse array, gene mutations, and amplifications and also as a consequence of its central role in several signal transduction pathways, the PI3K-dependent axis is frequently activated in many tumors and is an attractive therapeutic target. The preclinical testing and analysis of these novel therapies requires appropriate and well-tailored systems. Mouse models in which this pathway has been genetically modified have been essential in understanding the role that this pathway plays in the tumorigenesis process. Here, we review cancer mouse models in which the PI3K/AKT pathway has been genetically modified.