Overexpression of astrocyte-elevated gene-1 is associated with cervical carcinoma progression and angiogenesis
Overexpression of astrocyte-elevated gene-1 is associated with cervical carcinoma progression and angiogenesis
复制标题
星形胶质细胞升高基因 1 的过度表达与宫颈癌进展和血管生成相关
DOI：
10.3892/or.2013.2598
复制
发表时间：
2013-09-01
期刊：
影响因子：
4.2
通讯作者：
Zhang, Huizhong
中科院分区：
文献类型：
--
作者：
Long, Min;Dong, Ke;Zhang, Huizhong
星形胶质细胞上调基因-1(AEG-1)与多种人类肿瘤的发生和血管生成有关。然而，AEG-1在宫颈癌中的生物学作用仍有待进一步阐明。在本研究中，我们发现与正常宫颈上皮细胞(NCECs)相比，AEG-1在宫颈癌细胞系HeLa、CaSki和SIHA以及8对原发子宫颈癌组织(CCT)中的转录和翻译水平均显著上调。免疫组织化学分析显示90%(180/200)的宫颈鳞癌标本AEG-1表达阳性，统计学分析显示AEG-1表达上调与临床分期(P=0.034)、T分期(P=0.019)、N分期(P=0.038)、M分期(P=0.018)及肿瘤分化程度(P=0.043)显著相关。此外，功能丧失和功能获得的结果显示，特定shRNA下调AEG-1的表达不仅抑制了SIHA细胞的增殖和侵袭能力，而且显著降低了血管生成相关基因HIF-1α、Tie2、VEGF和TEM1/CD248的表达。此外，人脐静脉内皮细胞(HUVECs)与SIHA细胞和转导异位AEG-1的NCEs的条件培养液共培养后，血管形成能力均增强。这些结果提示，AEG-1的高表达在宫颈癌的侵袭性和血管生成中起重要作用，AEG-1是一种新的、有价值的预测宫颈癌患者预后的指标。
Astrocyte-elevated gene-1 (AEG-1) is implicated in the oncogenesis and angiogenesis of various types of human cancers. However, the biological roles of AEG-1 in cervical carcinoma remain to be further elucidated. In the present study, we demonstrated that the expression of AEG-1 was markedly upregulated in the cervical carcinoma cell lines HeLa, CaSki and SiHa, as well as in 8 paired primary cervical carcinoma tissue (CCT) specimens at both the transcriptional and translational levels when compared with normal cervical epithelial cells (NCECs). Furthermore, immunohistochemical (IHC) analysis demonstrated that 180 of 200 (90%) archived CCT specimens exhibited positive staining for AEG-1, and statistical analysis revealed that the upregulation of AEG-1 was significantly correlated with the clinical staging of the patients (P=0.034), including T (P=0.019), N (P=0.038) and M classification (P=0.018) as well as tumor differentiation (P=0.043). Furthermore, loss-and gain-of-function results showed that knockdown of AEG-1 expression by specific shRNA not only inhibited SiHa cell proliferation and invasive ability, but also significantly decreased the expression of the angiogenesis-related genes HIF-1 alpha, Tie2, VEGF and TEM1/CD248. Moreover, an increased vascular formation ability was observed in human umbilical vein endothelial cells (HUVECs) co-cultured with conditioned medium both from SiHa cells and NCECs transfected with ectopic AEG-1. In conclusion, these results suggest that elevated expression of AEG-1 plays an important role in the aggressiveness and angiogenesis of cervical carcinoma and that AEG-1 represents a novel and valuable predictive factor for the prognostic evaluation of cervical carcinoma patients.