Pathological angiogenesis is induced by sustained Akt signaling and inhibited by rapamycin
Pathological angiogenesis is induced by sustained Akt signaling and inhibited by rapamycin
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DOI：
10.1016/j.ccr.2006.07.003
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发表时间：
2006-08-01
期刊：
影响因子：
50.3
通讯作者：
Benjamin, Laura E.
中科院分区：
文献类型：
--
作者：
Phung, Thuy L.;Ziv, Keren;Benjamin, Laura E.
生长中的肿瘤中的内皮细胞表达活化的Akt，当通过myrAkt 1的转基因内皮表达来模拟时，其足以概括非肿瘤组织中肿瘤血管的异常结构和功能特征。持续的内皮Akt激活引起血管尺寸增加和慢性血管通透性引起的全身水肿，而响应于VEGF-A的急性通透性不受影响。这些变化是可逆的，表明持续需要Akt信号传导来维持这些表型。此外，雷帕霉素抑制内皮Akt信号传导、myrAkt 1引起的血管变化、肿瘤生长和肿瘤血管通透性。肿瘤血管间质中的Akt信号对雷帕霉素敏感，表明雷帕霉素可能部分通过作为血管Akt抑制剂影响肿瘤生长。
Endothelial cells in growing tumors express activated Akt, which when modeled by transgenic endothelial expression of myrAkt1 was sufficient to recapitulate the abnormal structural and functional features of tumor blood vessels in nontumor tissues. Sustained endothelial Akt activation caused increased blood vessel size and generalized edema from chronic vascular permeability, while acute permeability in response to VEGF-A was unaffected. These changes were reversible, demonstrating an ongoing requirement for Akt signaling for the maintenance of these phenotypes. Furthermore, rapamycin inhibited endothelial Akt signaling, vascular changes from myrAkt1, tumor growth, and tumor vascular permeability. Akt signaling in the tumor vascular stroma was sensitive to rapamycin, suggesting that rapamycin may affect tumor growth in part by acting as a vascular Akt inhibitor.