Journal
MEDICAL ONCOLOGY
Volume 30, Issue 1, Pages -Publisher
HUMANA PRESS INC
DOI: 10.1007/s12032-012-0383-9
Keywords
AEG-1; Lung cancer; Apoptosis; PI3K; Caspase-3; Bcl-2
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Funding
- Foundation of China National Natural Science [30900650/H1615, 81172232/H1615]
- Foundation of Guangdong Natural Science [9451008901002146]
- Fund for the Preceptorial Program of Higher Education, China [20090171120070]
- Guangzhou science and technology program [122010u1-E00621]
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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).
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