Markowska Anna, Pawałowska Monika, Lubin Jolanta, Markowska Janina
Department of Perinatology and Gynecology, Poznan University of Medical Sciences, Poland.
Department of Oncology, Poznan University of Medical Sciences, Poland.
Contemp Oncol (Pozn). 2014;18(3):143-8. doi: 10.5114/wo.2014.43154. Epub 2014 Jun 18.
Carcinogenesis is a multistage process, during which the activity of signalling pathways responsible for cell cycle regulation and division is disrupted which leads to inhibition of apoptosis and enhanced proliferation. Improper activation of Wnt/β-catenin and PI3K. Akt pathways play essential role in endometrial cancers (EC), mainly type I. Mutations in APC, axin or CTNBB1 may lead to β-catenin overactivation leading to excessive gene expression. PTEN inactivation, mutations in the PIK3CA or Akt result in increased transmission in the PI3K/Akt pathway, apoptosis inhibition, intensive cell division, mTOR excitation. In non-endometrioid cancers, key mutations include suppressor gene TP53 responsible for repairing damaged DNA or apoptosis initiation. Irregularities in gene P16, encoding a protein forming the p16-cyclinD/CDK-pRb have also been described. Understanding the complex relations between specific proteins taking part in signal transduction of the abovementioned pathways is key to research on drugs used in targeted therapy.
致癌作用是一个多阶段过程，在此过程中，负责细胞周期调控和分裂的信号通路的活性受到破坏，从而导致细胞凋亡受到抑制，增殖增强。Wnt/β-连环蛋白和PI3K/Akt通路的不当激活在子宫内膜癌（EC），主要是I型子宫内膜癌中起重要作用。APC、轴蛋白或CTNBB1中的突变可能导致β-连环蛋白过度激活，从而导致基因过度表达。PTEN失活、PIK3CA或Akt中的突变导致PI3K/Akt通路中的信号传递增加、细胞凋亡抑制、细胞密集分裂、mTOR激活。在非子宫内膜样癌中，关键突变包括负责修复受损DNA或启动细胞凋亡的抑癌基因TP53。也有关于编码形成p16-细胞周期蛋白D/细胞周期蛋白依赖性激酶-pRb的蛋白质的基因P16的异常描述。了解参与上述信号转导途径的特定蛋白质之间的复杂关系是靶向治疗药物研究的关键。
