PTEN induces apoptosis and cell cycle arrest through phosphoinositol-3-kinase/Akt-dependent and -independent pathways
PTEN induces apoptosis and cell cycle arrest through phosphoinositol-3-kinase/Akt-dependent and -independent pathways
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DOI：
10.1093/hmg/10.3.237
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发表时间：
2001-02-01
影响因子：
3.5
通讯作者：
Eng, C
中科院分区：
文献类型：
--
作者：
Weng, LP;Brown, JL;Eng, C
肿瘤抑制因子 PTEN 通过多种机制抑制细胞生长。我们之前已经证明，MCF-7 乳腺癌细胞中 PTEN 的过度表达会导致 G(1) 停滞，随后导致细胞死亡，后者被认为是由磷酸肌醇 3 激酶 (PI3K) 和 Akt/PKB 促凋亡途径介导的。在本研究中，我们表明，在存在低水平生长因子的情况下进行培养，通过增强 PTEN 诱导的细胞死亡来增加 PTEN 介导的生长抑制。 Caspase 9 特异性抑制剂 ZVAD 可阻断 PTEN 诱导的细胞死亡，而不改变 PTEN 对细胞周期分布的影响。根据表达水平，与过表达 PTEN 时对细胞死亡和细胞周期的影响相比，显性失活 Akt 的过表达诱导更多的细胞死亡并对细胞周期影响较小，或者诱导相似或减少的细胞死亡而不影响细胞周期。总而言之，这些观察结果表明，在 MCF-7 乳腺癌细胞中，PTEN 过表达诱导的凋亡细胞并非源自 G, 阻滞细胞。此外，PTEN 对细胞死亡的影响是通过 PI3K/Akt 途径介导的，而 PTEN 介导的细胞周期停滞是通过 PI3K/Akt 依赖性和非依赖性途径介导的。
The tumour suppressor PTEN inhibits cell growth through multiple mechanisms. We have previously demonstrated that overexpression of PTEN in MCF-7 breast cancer cells causes G(1) arrest followed by cell death, the latter of which is believed to be mediated by the phosphoinositol-3-kinase (PI3K) and Akt/PKB pro-apoptotic pathways. In this present study, we show that culture in the presence of low levels of growth factors increased PTEN-mediated growth suppression through the enhancement of PTEN-induced cell death. The caspase 9-specific inhibitor, ZVAD, blocked PTEN-induced cell death without altering the effect of PTEN on cell cycle distribution. Depending on the level of expression, overexpression of dominant-negative Akt induces more cell death and has less effect on the cell cycle or induces similar or decreased cell death without affecting the cell cycle compared with effects on cell death and the cell cycle when overexpressing PTEN, These observations in sum suggest that, in MCF-7 breast cancer cells, the apoptotic cells induced by the overexpression of PTEN did not derive from the G,arrested cells. Further, the effect of PTEN on cell death is mediated through the PI3K/Akt pathway whereas PTEN-mediated cell cycle arrests are through PI3K/Akt-dependent and -independent pathways.