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c-Fos高表达诱导恶性胶质瘤辐射抗拒并预测不良预后

High expression of c-Fos promotes radioresistance and predicts poor prognosis in malignant glioma

中文摘要英文摘要

c-Fos是激活蛋白的主要组成部分,与细胞分化、增殖、血管形成、侵袭和转移有关。在这项研究中,我们研究发现c-Fos对于脑胶质瘤放射敏感性的作用。在神经胶质瘤细胞系中通过慢病毒下调c-fos基因,我们分析了细胞增殖能力,DNA损伤修复能力,及细胞周期分布。最后,我们探讨c-Fos对于41例恶性胶质瘤患者的预后价值。我们的研究结果表明,抑制胶质瘤细胞c-Fos可增加辐射增加辐射诱导的DNA双链断裂(DSBs),干扰了DNA的损伤修复过程,促进G2细胞周期阻滞和凋亡。c-Fos蛋白表达与胶质瘤患者预后差相关。我们的研究结果为为恶性胶质瘤辐射抗拒提供了新的理论。c-Fos可能希望成为一个恶性胶质瘤患者的治疗新靶点。

c-Fos is a major component of activator protein (AP)-1 complex, which has been implicated in cell differentiation, proliferation, angiogenesis, invasion and metastasis. In this study, we investigated the role of c-Fos gene in glioma radiosensitivity and figured out the involved molecular mechanisms. Following downregulation of c-Fos gene by lenti-virus in glioma cell lines, we analyzed the radiosensitivity, DNA damage repair capacity, and cell cycle distribution of c-Fos. At last, we explored its prognostic value in 41 malignant glioma patients by immunohistochemistry. Our results showed that c-Fos inhibition could sensitize glioma cells to radiation by increasing radiation induced DNA double strand breaks(DSBs), disturbing the DNA damage repair process, promoting G2 cell cycle arrest and apoptosis. c-Fos protein overexpression correlated with poor prognosis in glioma patients who received standard treatment. Our findings provide new insights into the mechanism of radioresistance in malignant glioma. Therefore, c-Fos may hopefully become a novel therapeutic target for malignant glioma patients.

刘志刚、王晖

肿瘤学基础医学神经病学、精神病学

恶性胶质瘤,辐射抗拒,预后

Malignant Glioma Radioresistance c-Fos prognosis

刘志刚,王晖.c-Fos高表达诱导恶性胶质瘤辐射抗拒并预测不良预后[EB/OL].(2016-01-05)[2025-08-11].http://www.paper.edu.cn/releasepaper/content/201601-60.点此复制

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