Feedback inhibition of Akt signaling limits the growth of tumors lacking Tsc2
Feedback inhibition of Akt signaling limits the growth of tumors lacking Tsc2
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DOI：
10.1101/gad.1314605
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发表时间：
2005-08-01
影响因子：
10.5
通讯作者：
Cantley, LC
中科院分区：
文献类型：
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作者：
Manning, BD;Logsdon, MN;Cantley, LC
PTEN 和 TSC2 肿瘤抑制因子抑制哺乳动物雷帕霉素靶点 (mTOR) 信号传导，并且在不同的错构瘤综合征中存在缺陷。利用小鼠遗传学，我们发现 Pten 和 Tsc2 协同作用，抑制这些基因缺失所特有的一组肿瘤的严重程度。有趣的是，我们发现 Tsc2(+/-) 小鼠特有的缓慢生长的肿瘤在 Akt 下游信号传导方面表现出缺陷。然而，Pten 单倍体不足会恢复这些肿瘤中的 Akt 信号传导，并显着增强其严重程度。这项研究表明，缺乏 TSC2 的肿瘤中 PI3K-Akt 通路的减弱有助于其良性性质。
The PTEN and TSC2 tumor suppressors inhibit mammalian target of rapamycin (mTOR) signaling and are defective in distinct hamartoma syndromes. Using mouse genetics, we find that Pten and Tsc2 act synergistically to suppress the severity of a subset of tumors specific to loss of each of these genes. Interestingly, we find that the slow-growing tumors specific to Tsc2(+/-) mice exhibit defects in signaling downstream of Akt. However, Pten haploinsufficiency restores Akt signaling in these tumors and dramatically enhances their severity. This study demonstrates that attenuation of the PI3K-Akt pathway in tumors lacking TSC2 contributes to their benign nature.