Astrocyte Elevated Gene-1 Protein Expression Research Articles

Expression of astrocyte elevated gene-1 protein in ameloblastomas, keratocystic odontogenic tumors, and dentigerous cysts.

Benign epithelial odontogenic tumors such as ameloblastoma and keratocystic odontogenic tumor (KCOT) may exhibit an aggressive clinical course reminiscent of malignancies. Recent studies have indicated that astrocyte elevated gene-1 (AEG-1) is highly expressed in a variety of malignant neoplasms and its overexpression is associated with tumor invasion, metastasis, and poor survival. However, the role of AEG-1 in odontogenic tumors and cysts is still undiscovered. Immunohistochemical staining of AEG-1 was performed in 42 cases of ameloblastoma, 29 cases of KCOT, and 19 cases of dentigerous cyst. Correlations between AEG-1 expression and clinical parameters of ameloblastomas or KCOTs were statistically analyzed. AEG-1-positive staining was found in 37 (88%) of 42 ameloblastomas and in 24 (83%) of 29 KCOTs. None of 19 dentigerous cysts were positive for AEG-1 protein. For ameloblastomas, AEG-1 protein expression was significantly higher in ameloblast-like cells than in stellate reticulum-like cells (P = 0.003). For KCOTs, AEG-1 protein was diffusely expressed in all lining epithelial cells except the superficial parakeratinized cells. Moreover, the frequency of cortical plate perforation was significantly higher in ameloblastomas with high AEG-1 expression than in ameloblastomas with low or negative AEG-1 expression (P = 0.043). Significantly higher expression of AEG-1 protein in ameloblastomas and KCOTs than in dentigerous cysts and significantly greater frequency of cortical plate perforation in high AEG-1-expressed ameloblastomas than in low or negative AEG-1-expressed ameloblastomas may imply the high potential of AEG-1 to serve as a locally invasive biomarker and a target for novel therapy.

Expression and clinicopathological significance of miR-193a-3p and its potential target astrocyte elevated gene-1 in non-small lung cancer tissues.

BackgroundAberrant expression of miR-193a-3p and astrocyte elevated gene-1 (AEG-1) have been revealed to be related to the tumorigenesis of various cancers, including non-small cell lung cancer (NSCLC). However, the significance of miR-193a-3p and its correlation with AEG-1 in NSCLC has not been explored. The purpose of this study was to evaluate the association between miR-193a-3p and AEG-1 and their relationship with the clinicopathological features in NSCLC patients.MethodsVia online in silico prediction, complementary sequences were found between miR-193a-3p and the 3′-untranslated region of AEG-1. Three independent cohorts were applied in the current study. Firstly, miR-193a-3p level was detected in 125 cases of NSCLC with quantitative real-time PCR (qRT-PCR). Secondly, AEG-1 protein level was evaluated in 339 cases of lung cancers with immunohistochemistry. Finally, the relationship between miR-193a-3p and AEG-1 protein expression was verified in another group with 65 cases of NSCLC.ResultsThe results showed that miR-193a-3p level was decreased in NSCLC tissues and significantly negatively related to tumor size (r = −0.277, P = 0.002), clinical TNM stage (r = −0.226, P = 0.011), lymph node metastasis (r = −0.186, P = 0.038), epidermal growth factor receptor (EGFR) protein level (r = −0.272, P = 0.041). On the contrary, AEG-1 protein expression was up-regulated in NSCLC and positively relative to tumor size (r = 0.240, P < 0.001), TNM stages (r = 0.164, P = 0.002) and lymph node metastasis (r = 0.232, P < 0.001) in NSCLC patients. In addition, miR-193a-3p was found to be inversely associated with AEG-1 protein expression in the third cohort (r = −0.564, P < 0.001).ConclusionIn conclusion, miR-193a-3p and AEG-1 might be responsible for the carcinogenesis and aggressiveness of NSCLC. AEG-1 has the potential to be one of the targeted genes of miR-193a-3p. However, future in vitro and in vivo experiments are needed to verify this hypothesis.

Study on the effects of microRNA-375 on gastric cancer cell function

Objective To investigate the effects of microRNA(miRNA)-375 on gastric cancer cell function and the possible mechanism.Methods miRNA-375 eukaryotic expression vector was stably transfected into human gastric cancer cell line HGC-27.A miRNA-375 highly expressed gastric cancer cell line PC3,1-375 was screened and established.Blank plasmid transfection group (PC3.1 group) and blank control group were also established.The cell proliferation ability and apoptosis rate in three groups were detected by cell counting kit-8 (CCK-8) method and flow cytometry.The protein expression of astrocyte elevated gene 1 (AEG-1) in three groups was determined by Western blotting.The nude mouse subcutaneous xenografts model was also established.After 30 days,the nude mice were executed and the xenografts were dissociated and measured.The expression ofAEG-1 in the tumors at protein level was tested by immunohistochemistry method.The statistical inference includes t-test and analysis of variance.Results After stable transfection and cell screening,compared with that of blank control group,the expression of miRNA-375 in PC3.1-375 group significantly increased (t=2.82,2.01,bothP＜0.05).The cell proliferation of PC3.1-375 group was significantly lower than that of PC3.1 group and blank control group and the difference reached a maximum in day 3 (t3d=3.56,2.79,both P＜0.05).But with the apoptosis rate of PC3.1-375 group,the opposite was true (t=2.05,2.96,both P＜0.05).The results of Western blot shows that the expression of AEG-1 at protein level of PC3.1-375 group decreased compared with that of blank control group and PC3.1 group.The xenografts growth rate,average weight and tumor volume of PC3.1-375 group were significantly lower than those of blank control group and PC3.1 group (t=3.78,2.26,both P＜0.05).By the end of experiment,the volume of nude mouse subcutaneous xenografts in blank control group ((3.12 ± 0.77) cm3) and PC3.1 group ((3.76 ± 0.65) cm3) was significant bigger than that inPC3.1-375 group (0.72±0.21) cm3,t=5.67,6.92,both P＜0.05).The average weight of xenografts in PC3.1-375 group ((0.85 ± 0.15)g) was obviously lower than that in PC3.1 group ((4.01±0.52) g) and blank control group ((3.86±0.56) g,t=4.56,5.01,both P＜0.05).The results of immunohistochemistry indicated that the expression of AEG-1 protein in xenografts in PC3.1-375 group was remarkably decreased compared with that in blank control group and PC3.1 group (F=35.000,P＜0.05).Conclusions miRNA-375 can effectively inhibit the cell proliferation of gastric cancer,promote cells apoptosis and it's a tumor suppression factor in gastric cancer.AEG-1 may be a target gene of miRNA-375. Key words: Stomach neoplasms; MicroRNAs; Transfection; Cell proliferation; Apoptosis; Disease models, animal; Neoplasm seeding

Expression of astrocyte elevated gene-1 protein and its clinical significance in laryngeal squamous cell carcinoma

To assess the protein expression of astrocyte elevated gene-1 (AEG-1) in tissue specimens of laryngeal squamous cell carcinoma (LSCC), and to correlate its expression with clinicopathological parameters and prognosis in patients with LSCC. RT-PCR was used to assay the expression of AEG-1 mRNA in 13 pairs of LSCC tissues and their corresponding noncarcinoma epithelia. Immunohistochemistry was performed on paraffin-embedded tissue specimens to investigate the protein expression of AEG-1 in 88 cases of LSCC specimens and 15 cases of adjacent epithelial samples. The expression of AEG-1 mRNA was significantly increased in LSCC tissues compared to adjacent noncarcinoma epithelial tissues (0.81 ± 0.17 vs. 0.23 ± 0.10;t = 10.337, P < 0.001). Meantime, the positive rate of AEG-1 protein in 88 cases of LSCC was 87.5% (77/88). However, 15 cases of adjacent noncarcinoma epithelial merely demonstrated negative or mild expression of AEG-1 protein. AEG-1 overexpression was closely correlated with T stage (χ(2) = 6.289, P = 0.018), clinical stage (χ(2) = 11.049, P < 0.01), metastasis (χ(2) = 20.859, P < 0.01) and recurrence(χ(2) = 13.459, P < 0.01). The overall survival rates of patients with AEG-1 overexpression and low expression were 35.9% and 86.4%, respectively (χ(2) = 23.409, P < 0.01). Multivariate Cox regression analysis revealed that AEG-1 expression was an independent prognostic factor (P = 0.016). AEG-1 protein may play a critical role in the initiation and progression of LSCC, implicating its predictive value in prognosis.

Expression characteristics of astrocyte elevated gene-1 (AEG-1) in tongue carcinoma and its correlation with poor prognosis

Astrocyte elevated gene-1 (AEG-1) expression is increased in diverse human cancers and plays a vital role in tumorigenesis and progression. The aim of this study was to investigate the clinicopathologic features and prognostic significance of AEG-1 in squamous cell carcinoma of the tongue (TSCC). Immunohistochemistry (IHC) was performed to examine AEG-1 protein expression in paraffin-embedded tissues from 93 patients with TSCC. Real-time PCR and western blot analyses were employed to examine AEG-1 expression in 4 pairs of primary TSCC and adjacent non-cancerous tissues from the same patient. Immunohistochemical results revealed that the positive rate for AEG-1 in TSCC tissues (48.39%, 45/93) was higher than that in the normal tongue tissues (10.00%, 3/30) (P<0.001). These results were further confirmed between TSCC tissues and matched adjacent non-cancerous tissues by Western blot and RT-PCR. Simultaneously, AEG-1 protein level was positively correlated with differentiation degree (P<0.001), clinical stage (P<0.001), T classification (P=0.007) and N classification (P=0.012). Furthermore, patients with higher AEG-1 expression had shorter overall survival time. Multivariate analysis (Cox regression) also suggested that AEG-1 expression was an independent prognostic indicator for TSCC (P=0.043). Our results indicate that AEG-1 expression is closely associated with carcinogenesis and progression of TSCC, and may represent a novel and valuable predictor for prognostic evaluation of TSCC patients.

AEG-1 is associated with clinical outcome in neuroblastoma patients

Astrocyte elevated gene 1 (AEG-1), a novel gene that was cloned in 2002, has emerged in recent years as a potentially crucial mediator of tumor malignancy and aberrant elevation of AEG-1 expression frequently occurs in several human cancers, including breast cancer, prostate cancer, gastric cancer. However, whether AEG-1 deregulation also occurs in neuroblastoma remains unclear. In previous study we reported that AEG-1 was over expressed in neuroblastoma cell lines and knockdown of AEG-1 inhibits proliferation and enhancing chemo-sensitivity to cisplatin or doxorubicin in neuroblastoma cells. In this study, we investigated the expression of AEG-1 and evaluate its prognostic significance by correlating AEG-1 expression levels with clinic pathologic features and survival in 32 archived neuroblastoma patients We found that positive AEG-1 immunoreactivities were present in all neuroblastoma cases, 75% showed high expression of AEG-1. And high expression of AEG-1 was commonly seen in vascular endothelial cells and glandula in neuroblastoma samples. AEG-1 expression was strongly correlated with age at diagnosis (P=0.012), clinical stage (P=0.030) and tumor histology stage (P=0.041). However, our analyses did not show significant associations between AEG-1 expression and other clinical features including gender and primary tumor site. Importantly, our data presented in this report provide, for the first time, evidence that elevated expression of AEG-1 protein is correlated with poor prognosis and reduced survival of patients with neuroblastoma (P= 0.031). Overall, the data support the notion that AEG-1 might be used as a biomarker for neuroblastoma patients.

Astrocyte elevated gene-1 (AEG-1) is a marker for aggressive salivary gland carcinoma

BackgroundAstrocyte elevated gene-1 (AEG-1) is associated with tumorigenesis and progression in diverse human cancers. The present study was aimed to investigate the clinical and prognostic significance of AEG-1 in salivary gland carcinomas (SGC).MethodsReal-time PCR and western blot analyses were employed to examine AEG-1 expression in two normal salivary gland tissues, eight SGC tissues of various clinical stages, and five pairs of primary SGC and adjacent salivary gland tissues from the same patient. Immunohistochemistry (IHC) was performed to examine AEG-1 protein expression in paraffin-embedded tissues from 141 SGC patients. Statistical analyses was applies to evaluate the diagnostic value and associations of AEG-1 expression with clinical parameters.ResultsAEG-1 expression was evidently up-regulated in SGC tissues compared with that in the normal salivary gland tissues and in matched adjacent salivary gland tissues. AEG-1 protein level was positively correlated with clinical stage (P < 0.001), T classification (P = 0.008), N classification (P = 0.008) and M classifications (P = 0.006). Patients with higher AEG-1 expression had shorter overall survival time, whereas those with lower tumor AEG-1 expression had longer survival time.ConclusionsOur results suggest that AEG-1 expression is associated with SGC progression and may represent a novel and valuable predictor for prognostic evaluation of SGC patients.

Clinical significance of astrocyte elevated gene-1 expression in human oligodendrogliomas

Objective To investigate the expression of astrocyte elevated gene-1 (AEG-1) in human oligodendrogliomas and the association between AEG-1 expression and progression of oligodendrogliomas. Methods The expression of AEG-1 in normal human oligodendroglial cells, oligodendroglioma cell line, and four pairs of matched oligodendroglioma tissues and their adjacent normal brain tissues was detected by quantitative RT-PCR and western blotting. In addition, AEG-1 protein expression was examined in 75 cases of histologically characterized oligodendrogliomas by immunohistochemistry. Statistical analyses were applied to test for prognostic and diagnostic associations. Results Western blotting and RT-PCR showed that AEG-1 mRNA and protein were elevated in the oligodendroglioma cell line and significantly upregulated in primary oligodendrogliomas compared with the adjacent non-cancerous brain tissues. Immunohistochemical analysis showed that 51 of 75 (68.0%) paraffin-embedded archival oligodendroglioma samples exhibited high expression of AEG-1. Statistical analysis suggested that upregulation of AEG-1 was significantly correlated with the histological grade of oligodendroglioma ( p = 0.000) and that patients with high AEG-1 level exhibited shorter survival time ( p = 0.000). Multivariate analysis revealed that AEG-1 upregulation might be an independent prognostic indicator for the survival of patients with oligodendroglioma. Conclusions AEG-1 might represent a novel, useful diagnostic and prognostic marker for oligodendroglioma and play a role during the development and progression of the disease.

Astrocyte Elevated Gene-1: Far More Than Just a Gene Regulated in Astrocytes

Since its original cloning by subtraction hybridization in 2002, it is now evident that Astrocyte elevated gene-1 (AEG-1) is a key contributor to the carcinogenic process in diverse organs. AEG-1 protein expression is elevated in advanced stages of many cancers, which correlates with poor survival. In specific cancers, such as breast and liver cancer, the AEG-1 gene itself is amplified, further supporting a seminal role in tumorigenesis. Overexpression and inhibition studies both in in vitro and in in vivo models reveal the importance of AEG-1 in regulating multiple physiologically and pathologically relevant processes including proliferation, invasion, metastasis, and gene expression. AEG-1 is a single-pass transmembrane protein with multiple nuclear localization signals and no known domains or motifs. Although pertinent roles of AEG-1 in the carcinogenic process are established, its potential function (promotion of metastasis only versus functioning as a bona fide oncogene) as well as localization (cell surface versus nucleus) remain areas requiring further clarification. The present review critically evaluates what is currently known about AEG-1 and provides new perspectives relative to this intriguing molecule that may provide a rational target for intervening in the cancer phenotype.

Astrocyte Elevated Gene-1 is a Novel Prognostic Marker for Breast Cancer Progression and Overall Patient Survival

The present study was aimed at clarifying the expression of astrocyte elevated gene-1 (AEG-1), one of the target genes of oncogenic Ha-ras, in breast cancer and its correlation with clinicopathologic features, including the survival of patients with breast cancer. The expression of AEG-1 in normal breast epithelial cells, breast cancer cell lines, and in four cases of paired primary breast tumor and normal breast tissue was examined using reverse transcription-PCR and Western blot. Real-time reverse transcription-PCR was applied to determine the mRNA level of AEG-1 in the four paired tissues, each from the same subject. Furthermore, AEG-1 protein expression was analyzed in 225 clinicopathologically characterized breast cancer cases using immunohistochemistry. Statistical analyses were applied to test for the prognostic and diagnostic associations. Western blot and reverse transcription-PCR showed that the expression level of AEG-1 was markedly higher in breast cancer cell lines than that in the normal breast epithelial cells at both mRNA and protein levels. AEG-1 expression levels were significantly up-regulated by up to 35-fold in primary breast tumors in comparison to the paired normal breast tissue from the same patient. Immunohistochemical analysis revealed high expression of AEG-1 in 100 of 225 (44.4%) paraffin-embedded archival breast cancer biopsies. Statistical analysis showed a significant correlation of AEG-1 expression with the clinical staging of the patients with breast cancer (P = 0.001), as well as with the tumor classification (P = 0.004), node classification (P = 0.026), and metastasis classification (P = 0.001). Patients with higher AEG-1 expression had shorter overall survival time, whereas patients with lower AEG-1 expression had better survival. Multivariate analysis suggested that AEG-1 expression might be an independent prognostic indicator for the survival of patients with breast cancer. Our results suggest that AEG-1 protein is a valuable marker of breast cancer progression. High AEG-1 expression is associated with poor overall survival in patients with breast cancer.