Department of Medicine and Pathology, Harvard Medical School, Boston, MA 02215, USA.
Curr Top Microbiol Immunol. 2010;347:135-68. doi: 10.1007/82_2010_62.
A decade of work has indisputably defined PTEN as a pivotal player in human health and disease. Above all, PTEN has been identified as one of the most commonly lost or mutated tumor suppressor genes in human cancers. For this reason, the generation of a multitude of mouse models has been an invaluable strategy to dissect the function and consequences-of-loss of this essential, evolutionary conserved lipid phosphatase in tumor initiation and progression.In this chapter, we will summarize the mouse models that have allowed us to faithfully recapitulate features of human cancers and to highlight the network of connections between the PTEN signaling cascade and other oncogenic or tumor suppressive pathways.Notably, PTEN represents one of the most extensively modeled genes involved in human cancer and exemplifies the strength of genetic mouse modeling as an approach to gain information aimed to improve our understanding of and ability to alleviate human disease.
十年来的研究无可争议地将 PTEN 定义为人类健康和疾病的关键参与者。最重要的是,PTEN 已被确定为人类癌症中最常丢失或突变的肿瘤抑制基因之一。出于这个原因,生成大量的小鼠模型一直是一种非常宝贵的策略,可以解析这种必需的、进化上保守的脂质磷酸酶在肿瘤起始和进展中的功能和丧失后果。在本章中,我们将总结允许我们忠实地再现人类癌症特征的小鼠模型,并强调 PTEN 信号级联与其他致癌或肿瘤抑制途径之间的联系网络。值得注意的是,PTEN 是涉及人类癌症的最广泛建模基因之一,它体现了遗传小鼠建模作为一种获取旨在改善我们对人类疾病的理解和治疗能力的信息的方法的优势。