Endersby R, Baker S J
Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN 38105-2794, USA.
Oncogene. 2008 Sep 18;27(41):5416-30. doi: 10.1038/onc.2008.239.
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor that antagonizes the phosphatidylinositol-3-kinase (PI3K)/Akt/mTOR pathway by functioning as a lipid phosphatase. This ubiquitous and evolutionarily conserved signaling cascade influences numerous functions including cell growth, survival, proliferation, migration and metabolism. Inherited mutations in PTEN cause pleiotropic effects including cancer predisposition as well as a range of neurological abnormalities revealing specialized roles for PTEN in nervous system development and maintenance. Somatic mutations in PTEN occur frequently as late events in sporadic brain tumors. Mouse models based on Pten deletion in the brain have provided insights into the normal functions of Pten in the nervous system as well as the initiation and progression of gliomas. Compromised PTEN function may contribute to gliomagenesis through disrupted regulation of proliferation, migration, invasion, angiogenesis, stem cell self-renewal and regulation of other tumor suppressor pathways such as p53. Clinical findings in high-grade glioma suggest that PTEN gene alterations are associated with poor prognosis and may influence response to specific therapies. Emerging research using specific pharmacological inhibitors of the PI3K pathway may provide novel therapeutic options for the treatment of PTEN-deficient tumors.
10号染色体缺失的磷酸酶及张力蛋白同源物（PTEN）是一种肿瘤抑制因子，它作为脂质磷酸酶，拮抗磷脂酰肌醇-3-激酶（PI3K）/Akt/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路。这种广泛存在且在进化上保守的信号级联反应影响着众多功能，包括细胞生长、存活、增殖、迁移和代谢。PTEN的遗传性突变会导致多效性效应，包括癌症易感性以及一系列神经学异常，揭示了PTEN在神经系统发育和维持中的特殊作用。PTEN的体细胞突变在散发性脑肿瘤中经常作为晚期事件出现。基于大脑中Pten缺失的小鼠模型为了解Pten在神经系统中的正常功能以及胶质瘤的发生和发展提供了见解。PTEN功能受损可能通过扰乱增殖、迁移、侵袭、血管生成、干细胞自我更新的调控以及其他肿瘤抑制通路（如p53）的调控而导致胶质瘤的发生。高级别胶质瘤的临床研究结果表明，PTEN基因改变与预后不良相关，并可能影响对特定治疗的反应。使用PI3K通路特异性药理抑制剂的新兴研究可能为PTEN缺陷型肿瘤的治疗提供新的治疗选择。
