在白血病中PTEN的作用是由组织微环境决定的
Cornelius Miething1, Claudio Scuoppo2, Benedikt Bosbach3
11] Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA [2] Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA [3] Department of Medicine I, Medical Center - University of Freiburg, 79106 Freiburg, Germany.
Nature
|May 9, 2014
概括
损失PTEN瘤抑制基因促进T细胞急性淋巴细胞白血病. 重新激活PTEN减少了白血病的传播,但并没有减少瘤负担,突出显示了微环境在癌症进展中的作用.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 由于遗传变化,PTEN是一种关键的瘤抑制基因,在各种癌症中经常表达不充分.
- PTEN对抗PI3K/AKT/mTOR通路,这对于细胞生长和生存信号提供至关重要.
研究的目的:
- 调查持续的PTEN无活化是否对于维持癌症恶性瘤至关重要.
- 探索PTEN调节对T细胞急性淋巴细胞白血病 (T-ALL) 发展和进展的影响.
主要方法:
- 开发一种新型的转基因小鼠模型,具有四环素依赖的RNA干扰,用于时间和组织特定的PTEN调节.
- 产后的PTEN在造血区中被击倒,以诱导T-ALL.
- 对PTEN重新激活对白血病传播和瘤负载的影响的分析.
主要成果:
- 在血液细胞中产后的Pten敲击导致高度传播的T-ALL.
- PTEN的重新激活主要降低了T-ALL传播,对血液构成器官的瘤负担的影响最小.
- 白血病肠道透依赖于CCR9的信号传递,这种信号被PTEN损失所增强.
结论:
- 失去PTEN可以驱动瘤生长和入侵,可能是通过G蛋白结合受体信号传递,即使在具有挑战性的环境中.
- 瘤维护中的PTEN损失的作用取决于情境,并受到组织微环境的影响,有助于基因型独立的瘤内异质性.
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