Drosophila PTEN regulates cell growth and proliferation through PI3K-dependent and -independent pathways
Drosophila PTEN regulates cell growth and proliferation through PI3K-dependent and -independent pathways
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DOI：
10.1006/dbio.2000.9680
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发表时间：
2000-05-15
影响因子：
2.7
通讯作者：
Pan, DJ
中科院分区：
文献类型：
--
作者：
Gao, XS;Neufeld, TP;Pan, DJ
细胞和器官生长的控制是多细胞生物体发育的基础。在这里，我们表明，dPTEN，果蝇同源的哺乳动物PTEN肿瘤抑制基因，在控制细胞大小，细胞数量和器官大小中起着至关重要的作用。在嵌合体动物中，dPTEN（-）细胞比它们的杂合兄弟细胞增殖更快，显示出细胞大小的自主增加，并形成大小增加的器官，而dPTEN的过表达导致相反的表型。dPTEN的功能丧失表型受到PI 3 K靶点Dakt 1和翻译起始因子eif 4A突变的抑制，这表明dPTEN通过PI 3 K信号通路调节翻译。虽然PI 3 K和Akt的活化已被报道增加细胞生长而不是增殖的速率，但dPTEN的缺失刺激这两个过程，表明PTEN通过PI 3 K/Akt依赖性和非依赖性途径调节总体生长。此外，我们表明，dPTEN在果蝇发育过程中的细胞存活中不起主要作用。我们的结果为人类癌症中PTEN突变的高频率提供了潜在的解释。(C)北京大学出版社.
The control of cell and organ growth is fundamental to the development of multicellular organisms. Here, we show that dPTEN, a Drosophila homolog of the mammalian PTEN tumor suppressor gene, plays an essential role in the control of cell size, cell number, and organ size. In mosaic animals, dPTEN(-) cells proliferate faster than their heterozygous siblings, show an autonomous increase in cell size, and form organs of increased size, whereas overexpression of dPTEN results in opposite phenotypes. The loss-of-function phenotypes of dPTEN are suppressed by mutations in the PI3K target Dakt1 and the translational initiation factor eif4A, suggesting that dPTEN acts through the PI3K signaling pathway to regulate translation. Although activation of PI3K and Akt has been reported to increase rates of cellular growth but not proliferation, loss of dPTEN stimulates both of these processes, suggesting that PTEN regulates overall growth through PI3K/Akt-dependent and -independent pathways. Furthermore, we show that dPTEN does not play a major role in cell survival during Drosophila development. Our results provide a potential explanation for the high frequency of PTEN mutation in human cancer. (C) 2000 Academic Press.