PTEN/Cowden Multidisciplinary Clinic, Cleveland Clinic, Cleveland, OH 44195, USA.
Am J Med Genet C Semin Med Genet. 2013 May;163C(2):114-21. doi: 10.1002/ajmg.c.31364.
PTEN is a dual-specificity phosphatase and well-known tumor suppressor gene. When functioning properly, it works in its canonical pathway to inhibit AKT/mTOR and MAPK signaling, leading to cell death and growth regulation. PTEN mutations cause dysregulation of these pathways, resulting in cellular proliferation and overgrowth. When germline mutations are present as in patients with PTEN Hamartoma Tumor Syndrome (PHTS), benign and malignant neoplasias occur as well as cerebral overgrowth and neurodevelopmental abnormalities. This review article will summarize recent laboratory and clinical investigations relating to PTEN, highlighting the overgrowth aspects of this syndrome and the molecular drivers behind these key phenotypes. Finally, therapies developed targeted the PI3K/AKT/mTOR pathway for other tumor predisposition syndromes will be discussed.
PTEN 是一种双特异性磷酸酶，也是一种著名的肿瘤抑制基因。当它正常发挥作用时，它会在其经典途径中抑制 AKT/mTOR 和 MAPK 信号通路，从而导致细胞死亡和生长调节。PTEN 突变会导致这些通路失调，导致细胞增殖和过度生长。当存在种系突变，如患有 PTEN 错构瘤肿瘤综合征 (PHTS) 的患者，良性和恶性肿瘤以及大脑过度生长和神经发育异常都会发生。这篇综述文章将总结最近与 PTEN 相关的实验室和临床研究，重点介绍该综合征的过度生长方面以及这些关键表型背后的分子驱动因素。最后，还将讨论针对其他肿瘤易感性综合征开发的靶向 PI3K/AKT/mTOR 通路的疗法。
