mTOR promotes pituitary tumor development through activation of PTTG1
mTOR promotes pituitary tumor development through activation of PTTG1
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mTOR 通过激活 PTTG1 促进垂体瘤的发展
DOI：
10.1038/onc.2016.264
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发表时间：
2017-02-16
期刊：
影响因子：
8
通讯作者：
Zhang, H.
中科院分区：
文献类型：
--
作者：
Chen, R.;Duan, J.;Zhang, H.
垂体瘤是最常见的颅内肿瘤之一，发病率较高。由于垂体肿瘤发生的病理过程在很大程度上还不明确，目前还没有有效的治疗方法。在本研究中，观察到哺乳动物/雷帕霉素机械靶点(MTOR)信号通路在雌激素诱导的大鼠垂体瘤中高度激活，mTOR抑制剂雷帕霉素阻断了肿瘤的发展。基因敲除mTOR信号通路负调控因子TSC1或Pten均可引起小鼠垂体催乳素瘤，雷帕霉素可使其消失。机制上，垂体肿瘤转化基因1(Pttg1)的表达呈mTOR复合体1依赖性上调。过表达的Pttg1在高活性mTOR介导的肿瘤发生中起关键作用。MTOR-Pttg1信号轴可能成为治疗mTOR高激活肿瘤的靶点。
As one of the most common intracranial tumors, pituitary tumor is associated with high morbidity. Effective therapy is currently not available for some pituitary tumors due to the largely undefined pathological processes of pituitary tumorigenesis. In this study, hyperactivation of mammalian/mechanistic target of rapamycin (mTOR) signaling was observed in estrogen-induced rat pituitary tumor and mTOR inhibitor rapamycin blocked the tumor development. Pituitary knockout of either mTOR signaling pathway negative regulator Tsc1 or Pten caused mouse pituitary prolactinoma, which was abolished by rapamycin treatment. Mechanistically, the expression of pituitary tumor transforming gene 1 (PTTG1) was upregulated in an mTOR complex 1-dependent manner. Overexpressed PTTG1 was crucial in hyperactive mTOR-mediated tumorigenesis. mTOR-PTTG1 signaling axis may be targeted for the treatment of tumors with mTOR hyperactivation.