Marino Silvia, Krimpenfort Paul, Leung Carly, van der Korput Hetty A G M, Trapman Jan, Camenisch Isabelle, Berns Anton, Brandner Sebastian
Institute of Pathology, University Hospital, 8091 Zurich, Switzerland.
Development. 2002 Jul;129(14):3513-22. doi: 10.1242/dev.129.14.3513.
PTEN is a tumour suppressor gene involved in cell cycle control, apoptosis and mediation of adhesion and migration signalling. Germline mutations of PTEN in humans are associated with familial tumour syndromes, among them Cowden disease. Glioblastomas, highly malignant glial tumours of the central nervous system frequently show loss of PTEN. Recent reports have outlined some aspects of PTEN function in central nervous system development. Using a conditional gene disruption approach, we inactivated Pten in mice early during embryogenesis locally in a region specific fashion and later during postnatal development in a cell-specific manner, to study the role of PTEN in differentiation, migration and neoplastic transformation. We show that PTEN is required for the realisation of normal cerebellar architecture, for regulation of cell and organ size, and for proper neuronal and glial migration. However, PTEN is not required for cell differentiation and lack of PTEN is not sufficient to induce neoplastic transformation of neuronal or glial cells
PTEN是一种肿瘤抑制基因,参与细胞周期调控、细胞凋亡以及黏附与迁移信号的介导。人类PTEN的种系突变与家族性肿瘤综合征相关,其中包括考登病。胶质母细胞瘤是中枢神经系统的高度恶性胶质肿瘤,常表现出PTEN缺失。最近的报告概述了PTEN在中枢神经系统发育中的一些功能方面。我们采用条件性基因敲除方法,在胚胎发育早期以区域特异性方式局部敲除小鼠中的Pten,并在出生后发育阶段以细胞特异性方式敲除,以研究PTEN在分化、迁移和肿瘤转化中的作用。我们发现,PTEN对于正常小脑结构的形成、细胞和器官大小的调节以及神经元和胶质细胞的正常迁移是必需的。然而,细胞分化并不需要PTEN,PTEN的缺失也不足以诱导神经元或胶质细胞的肿瘤转化。