Regulation of angiogenesis and tumor growth by p110 alpha and AKT1 via VEGF expression
Regulation of angiogenesis and tumor growth by p110 alpha and AKT1 via VEGF expression
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DOI：
10.1002/jcp.20707
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发表时间：
2006-10-01
影响因子：
5.6
通讯作者：
Jiang, Bing-Hua
中科院分区：
文献类型：
--
作者：
Xia, Chang;Meng, Qiao;Jiang, Bing-Hua
近年来的研究表明，PI3K激活和PTEN突变在人类许多癌细胞和组织中都很常见。然而，PI3K信号在人类肿瘤发生中的作用机制尚不清楚。在这项研究中，我们使用siRNA干扰特异性下调卵巢癌细胞中p110 α的表达。我们发现p110 α下调可显著抑制卵巢肿瘤的生长和血管生成，p110 α siRNA通过降低卵巢癌细胞和肿瘤组织中缺氧诱导因子1 α的表达抑制VEGF的表达。为了确定PI3K调节肿瘤生长和血管生成的下游靶点，我们发现AKT1是调节肿瘤生长、血管生成和VEGF表达的主要下游介质。这些数据表明p110 α和AKT1通过诱导血管生成和增加HIF-1 α和VEGF表达在肿瘤生长中发挥重要作用。这项工作为更好地理解PI3K信号激活诱导人类癌症的分子机制提供了依据。
Recent studies demonstrate that PI3K activation and PTEN mutation are frequently found in many human cancer cells and tissues. However, the mechanism of PI3K signaling in human cancer tumorigenesis remains to be elucidated. In this study we specifically downregulated p110 alpha expression in ovarian cancer cells using siRNA interference. We found that p110 alpha downregulation greatly decreased ovarian tumor growth and angiogenesis, and that p110 alpha siRNA inhibited VEGF expression through decreasing hypoxia-inducible factor 1 alpha expression in both ovarian cancer cells and tumor tissues. To determine the downstream targets of PI3K in regulating tumor growth and angiogenesis, we find that AKT1 is a major downstream mediator for regulating tumor growth, angiogenesis, and VEGF expression. These data show that p110 alpha and AKT1 play an important role in tumor growth by inducing angiogenesis and by increasing HIF-1 alpha and VEGF expression. This work provides a better understanding of the molecular mechanism of human cancer induced by the activation of PI3K signaling.