Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Road 58, Guangzhou 510080, Province Guangdong, People's Republic of China.
Med Oncol. 2013 Mar;30(1):383. doi: 10.1007/s12032-012-0383-9. Epub 2013 Jan 10.
Expression of astrocyte-elevated gene-1 (AEG-1), a novel oncoprotein, has been shown to promote cell growth and inhibit apoptosis, but the underlying molecular mechanisms and its functional significance in non-small cell lung cancer (NSCLC) remain to be elucidated. In the present study, statistical analysis displayed a significant correlation of AEG-1 expression with clinical staging (P = 0.048), differentiation (P = 0.019) and lymph node metastasis (P = 0.032). Simultaneously, the overall survival time in patients with higher AEG-1 expression was obviously shorter than that in patients with lower expression of AEG-1 (P < 0.001). Furthermore, we found that AEG-1 could inhibit apoptotic cell death in L-78 cells, as assessed by MTT, TUNEL and flow cytometry assay. After treating L-78 cells with AEG-1 siRNA, caspase-3 protein was significantly up-regulated and Bcl-2 protein was markedly decreased in L-78 cells, which was verified by the immunohistochemistry results about AEG-1, caspase-3 and Bcl-2. Furthermore, PI3K p110 protein and phosphorylated Akt were also largely attenuated by the treatment of AEG-1 siRNA. In conclusion, our results indicated that AEG-1 played a crucial role in the carcinogenesis of NSCLC and could inhibit apoptosis via activating cell survival signaling (enhancing the level of anti-apoptotic protein Bcl-2 and the activation of PI3K/Akt pathway).
星形细胞上调基因-1（AEG-1）的表达已被证明可促进细胞生长并抑制细胞凋亡，但在非小细胞肺癌（NSCLC）中，其潜在的分子机制及其功能意义仍有待阐明。在本研究中，统计学分析显示 AEG-1 的表达与临床分期（P = 0.048）、分化（P = 0.019）和淋巴结转移（P = 0.032）显著相关。同时，AEG-1 高表达患者的总生存时间明显短于 AEG-1 低表达患者（P < 0.001）。此外，我们发现 AEG-1 可通过 MTT、TUNEL 和流式细胞术评估抑制 L-78 细胞的凋亡性细胞死亡。用 AEG-1 siRNA 处理 L-78 细胞后，L-78 细胞中的 caspase-3 蛋白明显上调，Bcl-2 蛋白明显下调，这一点通过 AEG-1、caspase-3 和 Bcl-2 的免疫组化结果得到了验证。此外，AEG-1 siRNA 的处理还大大减弱了 PI3K p110 蛋白和磷酸化 Akt 的水平。总之，我们的结果表明，AEG-1 在 NSCLC 的发生发展中起着关键作用，可通过激活细胞存活信号（增加抗凋亡蛋白 Bcl-2 的水平和激活 PI3K/Akt 通路）来抑制细胞凋亡。
