• Human pathology · Jul 2012

    Overexpression of astrocyte-elevated gene-1 is closely correlated with poor prognosis in human non-small cell lung cancer and mediates its metastasis through up-regulation of matrix metalloproteinase-9 expression.

    • Shijun Sun, Zunfu Ke, Fen Wang, Shuhua Li, Wenfang Chen, Anjia Han, Zuo Wang, Huijuan Shi, Lian-Tang Wang, and Xiaodong Chen.
    • Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Province Guangdong 510080, People's Republic of China.
    • Hum. Pathol. 2012 Jul 1;43(7):1051-60.

    AbstractExpression of astrocyte-elevated gene-1, a novel oncoprotein, is elevated in multiple cancers and plays a vital role in tumor cell growth, invasion, angiogenesis, and progression to metastasis. However, the functional significance of astrocyte-elevated gene-1 in non-small cell lung cancer still remains unclear. Our present study showed that the markedly up-regulated expression of astrocyte-elevated gene-1 was observed in non-small cell lung cancer cell lines and tissues at the level of both transcription and translation. Simultaneously, ectopic expression or small interfering RNA silencing of astrocyte-elevated gene-1 markedly enhanced or inhibited the invasive ability of non-small cell lung cancer cells, respectively. At the molecular level, we also revealed that the function of astrocyte-elevated gene-1 in promoting metastasis was associated with the activation of matrix metalloproteinase-9 expression. Consistent with these observations, immunostaining analysis revealed a significant positive correlation between astrocyte-elevated gene-1 and matrix metalloproteinase-9. Moreover, subcutaneous xenografts of non-small cell lung cancer cells engineered to express astrocyte-elevated gene-1 were highly invasive compared with the parental cells and expressed a high level of matrix metalloproteinase-9. In archival non-small cell lung cancer specimens, high astrocyte-elevated gene-1 expression correlated significantly with clinical staging (P = .048), differentiation (P = .023), and lymph node metastasis (P = .032). The overall survival time in patients with high astrocyte-elevated gene-1 expression was notably shorter than that in patients with low astrocyte-elevated gene-1 expression (P < .001). Taken together, our results indicate that astrocyte-elevated gene-1 plays a crucial role in the carcinogenesis and aggressiveness of non-small cell lung cancer, promoting its metastasis by modulating matrix metalloproteinase-9 expression and leading to a poor clinical prognosis.Copyright © 2012 Elsevier Inc. All rights reserved.

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