PTEN negatively regulates neural stem cell self-renewal by modulating G0-G1 cell cycle entry
PTEN negatively regulates neural stem cell self-renewal by modulating G0-G1 cell cycle entry
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DOI：
10.1073/pnas.0509939103
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发表时间：
2006-01-03
影响因子：
11.1
通讯作者：
Wu, H
中科院分区：
文献类型：
--
作者：
Groszer, M;Erickson, R;Wu, H
先前的研究已经证明，一小部分脑肿瘤细胞亚群在表型和行为方面与神经干/祖细胞具有关键特征。这些发现表明，脑肿瘤可能含有对肿瘤生长至关重要的“癌症干细胞”。然而，控制这种干细胞样行为的分子途径在很大程度上仍然难以捉摸。我们以前的研究表明，在胶质母细胞瘤中最常见的突变基因之一，10号染色体上的磷酸酶和张力蛋白同源物缺失（PTEN）肿瘤抑制基因，限制了体内神经干/祖细胞的增殖。在本研究中，我们试图确定PTEN在长期维持干细胞样特性、细胞周期进入和进展、生长因子依赖性和基因表达中的作用。我们的研究结果表明，增强自我更新能力和GO-G，细胞周期进入和减少生长因子依赖性的Pten空神经/干祖细胞。因此，PTEN的缺失导致细胞生理变化，这些变化共同足以增加自我更新神经干细胞的库并促进它们从增殖控制的稳态机制中逃逸。
Previous studies have demonstrated that a small subpopulation of brain tumor cells share key characteristics with neural stem/progenitor cells in terms of phenotype and behavior. These findings suggest that brain tumors might contain "cancer stem cells" that are critical for tumor growth. However, the molecular pathways governing such stem cell-like behavior remain largely elusive. Our previous study suggests that the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) tumor suppressor gene, one of the most frequently mutated genes in glioblastomas, restricts neural stem/progenitor cell proliferation in vivo. In the present study, we sought to determine the role of PTEN in long-term maintenance of stem cell-like properties, cell cycle entry and progression, and growth factor dependence and gene expression. Our results demonstrate an enhanced self-renewal capacity and GO-G, cell cycle entry and decreased growth factor dependency of Pten null neural/stem progenitor cells. Therefore, loss of PTEN leads to cell physiological changes, which collectively are sufficient to increase the pool of self-renewing neural stem cells and promote their escape from the homeostatic mechanisms of proliferation control.