Division of Oncology, Department of Clinical and Experimental Medicine, University of Linköping, Linköping, Sweden.
J Transl Med. 2012 May 29;10:109. doi: 10.1186/1479-5876-10-109.
Astrocyte elevated gene 1 (AEG-1), an important oncogene, has been shown to be overexpressed in several types of cancers. In colorectal cancer (CRC), the protein level of AEG-1 is up-regulated in tumour tissue compared to normal mucosa, showing prognostic significance. Since little is known about the transcriptional level of AEG-1 expression and its biological pathway in CRC the aim of the present study was to examine the relationship of AEG-1 mRNA expression, the protein level and clinicopathological variables as well as its biology pathway in CRC.
The mRNA expression of AEG-1 was analysed by qPCR in fresh frozen patient samples including 156 primary tumours, along with the corresponding normal mucosa, and in five colon cancer cell lines, SW480, SW620, KM12C, KM12SM and KM12L4a. AEG-1 protein expression was investigated by immunohistochemistry in paraffin-embedded materials from 74 distant normal mucosa, 107 adjacent mucosa, 158 primary tumour, 35 lymph node metastasis and 9 liver metastasis samples. In addition, the AEG-1 protein expression was elucidated in the cell lines by Western blot.
The lymph node metastatic cell line SW620 had a significantly higher AEG-1 mRNA (0.27 ± 0.02) expression compared to the primary tumour cell line SW480 (0.17 ± 0.04, p = 0.026). AEG-1 expression at the mRNA level and/or the protein level was significantly up-regulated gradually from normal mucosa to primary CRC, and then to lymph node metastasis and finally to liver metastasis (p < 0.05). There were significant associations of AEG-1 mRNA expression with tumour location (p = 0.047), as well as mRNA and protein expression with the tumour stage (p < 0.03). Furthermore AEG-1 protein expression was positively related to biological variables including NF-κB, p73, Rad50 and apoptosis (p < 0.05).
AEG-1 is up-regulated, at the mRNA and the protein level, during CRC development and aggressiveness, and is related to tumour location and stage. It may play its role in CRC through the NF-κB signaling pathway.
星形细胞上调基因 1（AEG-1）是一种重要的癌基因，已在多种类型的癌症中显示出过度表达。在结直肠癌（CRC）中，与正常黏膜相比，肿瘤组织中 AEG-1 的蛋白水平上调，具有预后意义。由于对 CRC 中 AEG-1 表达的转录水平及其生物学途径知之甚少，本研究旨在研究 AEG-1 mRNA 表达、蛋白水平与临床病理变量及其生物学途径的关系。
通过 qPCR 分析新鲜冷冻的患者样本中的 AEG-1mRNA 表达，包括 156 例原发性肿瘤，以及相应的正常黏膜，和 5 种结肠癌细胞系，SW480、SW620、KM12C、KM12SM 和 KM12L4a。通过免疫组织化学方法检测石蜡包埋材料中 74 个远处正常黏膜、107 个相邻黏膜、158 个原发性肿瘤、35 个淋巴结转移和 9 个肝转移样本中的 AEG-1 蛋白表达。此外，通过 Western blot 法阐明了 AEG-1 蛋白在细胞系中的表达。
淋巴结转移细胞系 SW620 的 AEG-1mRNA（0.27±0.02）表达明显高于原发性肿瘤细胞系 SW480（0.17±0.04，p=0.026）。AEG-1 的表达在 mRNA 水平和/或蛋白水平上从正常黏膜逐渐升高至原发性 CRC，然后升高至淋巴结转移，最后升高至肝转移（p<0.05）。AEG-1mRNA 表达与肿瘤部位（p=0.047）以及 mRNA 和蛋白表达与肿瘤分期（p<0.03）有显著相关性。此外，AEG-1 蛋白表达与 NF-κB、p73、Rad50 和凋亡等生物学变量呈正相关（p<0.05）。
AEG-1 在 CRC 的发生和侵袭过程中，在 mRNA 和蛋白水平上均上调，并与肿瘤部位和分期有关。它可能通过 NF-κB 信号通路在 CRC 中发挥作用。
