The inducible expression of the tumor suppressor gene PTEN promotes apoptosis and decreases cell size by inhibiting the PI3K/Akt pathway in Jurkat T cells.

The inducible expression of the tumor suppressor gene PTEN promotes apoptosis and decreases cell size by inhibiting the PI3K/Akt pathway in Jurkat T cells.
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发表时间:
2002-07
期刊:
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research
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通讯作者:
Zheng Xu;D. Stokoe;L. Kane;A. Weiss
Zheng Xu;D. Stokoe;L. Kane;A. Weiss
中科院分区:
其他
文献类型:
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作者:
Zheng Xu;D. Stokoe;L. Kane;A. Weiss

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在这项研究中,我们研究了抑癌基因PTEN在Jurkat T细胞中的功能。我们建立了稳定的Jurkat T细胞克隆,可以诱导表达野生型或磷酸酶失活的PTEN。我们在这里展示了PTEN有效地抑制了Jurkat细胞的生长并减小了其大小。PTEN的生长抑制作用与其诱导细胞凋亡的能力有关,而对细胞周期几乎没有影响。PTEN还使Jurkat细胞更容易受到各种刺激诱导的凋亡。此外,PTEN的表达导致3‘-磷酸化磷脂水平降低,从而改变Akt的活性和定位。最后,成分活性Akt的共表达逆转了PTEN的作用。综上所述,我们的结果表明,PTEN通过负向调节Jurkat T细胞中的肌醇磷脂3-激酶/Akt通路,抑制细胞生长,促进细胞凋亡,缩小细胞大小。
In this study, we characterize the function of the tumor suppressor gene PTEN in Jurkat T cells. We established stable clones of Jurkat T cells that inducibly express either wild-type or phosphatase-inactive PTEN. We show here that PTEN potently inhibited the growth and reduced the size of Jurkat cells. The growth-suppressive effect of PTEN was associated with its ability to induce apoptotic cell death with little or no effect on cell cycle. PTEN also rendered Jurkat cells more susceptible to apoptosis induced by various stimuli. Furthermore, PTEN expression led to a reduction in the level of 3'-phosphorylated phospholipids and thus altered the activity and localization of Akt. Finally, coexpression of constitutively active Akt reversed the effects caused by PTEN. In summary, our results suggest that PTEN suppresses cell growth, promotes apoptosis, and decreases cell size by negatively regulating the phosphoinositide 3-kinase/Akt pathway in Jurkat T cells.