AEG-1 expression characteristics in human non-small cell lung cancer and its relationship with apoptosis
AEG-1 expression characteristics in human non-small cell lung cancer and its relationship with apoptosis
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AEG-1在人非小细胞肺癌中的表达特征及其与细胞凋亡的关系
DOI：
10.1007/s12032-012-0383-9
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发表时间：
2013-03-01
期刊：
影响因子：
3.4
通讯作者：
Wang, Lian-tang
中科院分区：
文献类型：
--
作者：
Ke, Zun-fu;Mao, Xiaopeng;Wang, Lian-tang
星形胶质细胞上调基因-1(AEG-1)是一种新的癌蛋白，具有促进细胞生长和抑制细胞凋亡的作用，但其在非小细胞肺癌(NSCLC)中的分子机制及其功能意义尚不清楚。统计分析显示，AEG-1的表达与临床分期(P=0.048)、分化程度(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期明显短于AEG-1低表达患者(P<；0.001)。此外，通过四甲基偶氮唑盐比色法、原位末端标记法和流式细胞仪检测，我们发现AEG-1能够抑制L-78细胞的凋亡。AEG-1siRNA作用于L-78细胞后，Caspase-3蛋白表达明显上调，而Bcl一2蛋白表达明显降低，免疫组织化学结果证实了这一点。此外，AEG-1 siRNA处理后，PI3K p110蛋白和磷酸化Akt的表达也显著减弱。综上所述，我们的结果表明AEG-1在NSCLC的发生发展中起重要作用，并可能通过激活细胞生存信号(上调抗凋亡蛋白Bcl2的水平和激活PI3K/Akt通路)来抑制细胞凋亡。
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).