Expression of AEG-1 mRNA and protein in colorectal cancer patients and colon cancer cell lines

Abstract

BackgroundAstrocyte 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.Material and methodsThe 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.ResultsThe 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).ConclusionAEG-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.

AEG-1 expression is an independent prognostic factor in rectal cancer patients with preoperative radiotherapy: a study in a Swedish clinical trial

“…Moreover, we found that AEG-1 expression was not related to patient survival in CRC (Gnosa et al , 2012). Further survival analysis on the same cohort revealed no correlation of the AEG-1 expression with survival in either colon cancer patients or in rectal cancers patients (S Gnosa, unpublished data).…”

“…The AEG-1 is markedly overexpressed in many types of cancers compared with normal cells, including oesophageal squamous cell carcinoma (Yu et al , 2009), gastric cancer (Jian-bo et al , 2011), CRC (Gnosa et al , 2012), hepatocellular carcinoma (Yoo et al , 2009), non-small-cell lung cancer (Song et al , 2009), neuroblastoma (Lee et al , 2009), breast cancer (Brown and Ruoslahti, 2004; Li et al , 2008), prostate cancer (Thirkettle et al , 2009), and renal cancer (Chen et al , 2010). …”

Astrocyte elevated gene-1 (AEG-1) and the A(E)Ging HIV/AIDS-HAND

“…AEG-1 overexpression suppressed apoptosis by regulating phosphorylation of Akt substrates glycogen synthase kinase 3β, c-Myc, p53, and B-cell lymphoma-2 associated death promoter (Lee et al , 2008). AEG-1 was also induced after DNA damage and implicated in p53 independent apoptotic pathway by activating NF-κB (Gnosa et al , 2012). Additionally, opening of mitochondrial transition pores, an indicator of cell death, is enhanced in tissues of aged mice (Mather and Rottenberg, 2000).…”

Aeg-1/MTDH/Lyric

“…Gnosa et al (2012) analyzed AEG-1/MTDH/LYRIC mRNA expression by qPCR in primary tumor and adjacent normal mucosa from 156 CRC patients, and AEG-1/MTDH/LYRIC protein expression by IHC in 74 distant normal colorectal mucosa, 107 adjacent normal colorectal mucosa, 158 primary CRC, 35 lymph node metastases, and 9 liver metastases. The mean level of AEG-1/MTDH/LYRIC mRNA was 371.56±348.37 in the primary tumor and 214.98±156.39 in the adjacent normal mucosa in 156 patients ( p =0.0005).…”