An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/- mice
An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/- mice
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DOI：
10.1073/pnas.171060098
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发表时间：
2001-08-28
影响因子：
11.1
通讯作者：
Parsons, R
中科院分区：
文献类型：
--
作者：
Podsypanina, K;Lee, RT;Parsons, R
PTEN磷酸酶通过负调节磷酸肌醇3-激酶（PI3K）信号通路来充当肿瘤抑制器。目前尚不清楚该途径的哪种下游成分对于致癌转化是必需的。在本报告中，我们表明，PTEN +/-小鼠的转化细胞具有磷酸化的Akt水平升高，并激活了与增殖增加有关的P70/S6激酶。 MTOR/RAFT/FRAP的药理灭活可降低肿瘤增殖，肿瘤大小和P70/S6激酶活性，但不影响AKT的状态。这些数据表明，p70/S6K以及MTOR的其他靶标有显着贡献肿瘤的发育，并且对这些蛋白质的抑制可能对疾病的PI3K信号传导的癌症患者具有治疗性。
PTEN phosphatase acts as a tumor suppressor by negatively regulating the phosphoinositide 3-kinase (PI3K) signaling pathway. It is unclear which downstream components of this pathway are necessary for oncogenic transformation. In this report we show that transformed cells of PTEN+/- mice have elevated levels of phosphorylated Akt and activated p70/S6 kinase associated with an increase in proliferation. Pharmacological inactivation of mTOR/RAFT/FRAP reduced neoplastic proliferation, tumor size, and p70/S6 kinase activity, but did not affect the status of Akt. These data suggest that p70/S6K and possibly other targets of mTOR contribute significantly to tumor development and that inhibition of these proteins may be therapeutic for cancer patients with deranged PI3K signaling.