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Astrocyte elevated gene-1 (AEG-1) is a positive regulator of tumorigenesis in human cancer cells. Human AEG-1 gene is located in chromosome 8q22 having 12 exons/11 introns. Chromosome 8q22 is known to be a hot spot for genomic alterations in several cancerous cells involving HCC. The aim of the study was assess association between the negative regulatory region of AEG-1 promoter mutations and genetic susceptibility to hepatocellular carcinoma. The negative regulatory region of the human AEG-1 promoter was evaluated in a total of 50 Iranian hepatocellular carcinomas (HCC) patients. For investigating AEG-1 promoter polymorphisms the PCR-sequencing method was used. In this study was found two new mutation C>T (-633) and G>C (-660) in the patient group. But it was not revealed the statistically significant association between any mutations in this region of the AEG-1 promoter with HCC susceptibility. According to presented data, we can say that the negative regulatory region of the AEG-1 promoter mutations did not exihibit significant relevance with hepatocellular carcinoma. We recommend further studies on the efficacy of the AEG-1 promoter in therapeutic targeting of the HCC.
Resumo: O gene AEG-1 é um regulador positivo da tumorigênese em células cancerígenas humanas. O gene humano AEG-1 está localizado no cromossomo 8q22 com 12 exons/11 introns. O cromossomo 8q22 é conhecido por ser um hotspot para alterações genômicas em várias células cancerígenas que envolvem o CHC. O objetivo do estudo foi avaliar a associação entre a região reguladora negativa das mutações do promotor AEG-1 e a suscetibilidade genética ao carcinoma hepatocelular. A região reguladora negativa do promotor humano AEG-1 foi avaliada em um total de 50 pacientes iranianos com carcinomas hepatocelulares (CHC). Para investigar os polimorfismos do promotor AEG-1, utilizou-se o método de sequenciação por PCR. Neste estudo foram encontradas duas novas mutações C>T (-633) e G>C (-660) no grupo de pacientes. Mas não foi revelada a associação estatisticamente significante entre quaisquer mutações nessa região do promotor AEG-1 com suscetibilidade ao CHC. De acordo com os dados apresentados, podemos dizer que a região reguladora negativa das mutações do promotor AEG-1 não demonstrou relevância significativa com o carcinoma hepatocelular. Recomendamos estudos adicionais sobre a eficácia do promotor AEG-1 no direcionamento terapêutico do CHC.
Subject(s)
Patients , Astrocytes , Carcinoma, Hepatocellular , Genetic Predisposition to Disease , CarcinogenesisABSTRACT
Objective To investigate the effects of lentivirus-mediated knockdown of astrocyte elevated gene-1 (AEG-1) on the biological behavior of uveal melanoma(UM).Methods MUM-2B and MUM-2C cell lines with different invasiveness and metastasis potential were cultured.Based on AEG-1 sequence that designed the effective (RNA interference) RNAi target sequence and the RNAi negative control scramble sequence,and then performed the preparation of the lentiviral vector and viral packaging.In these two kinds of cell lines,the cells infected by AEG-1-RNAi lentivirus were used as lentiviral infection group,the cells of the RNAi negative control of the blank lentivirus infected cells were used as negative control group,and the cells without any processing were used as normal control group.Real-time PCR and Western blot were used to detect the change of AEG-1 transcription and protein expression levels in these two kinds of cell lines' groups,as well as by MTT method,Annexin V-APC method,cell invasion assay,and Transwell cell migration assay that to investigate the effect of lentivirus transfection induced knockdown of AEG-1 on the biological behavior of human UM cell lines.Results The successful preparation of RNAi lentivirus vector and its viral package were transfected to MUM-2B,MUM-2C cell lines of logarithmic growth phase,respectively.The relative expressions of AEG-1 mRNA in normal control groups,negative control groups and lentiviral infection groups were statistically significant (F =130.02,P＜0.01;F =144.17,P＜0.01).The relative expression of AEG-1 mRNA in lentiviral infection groups were lower than that in the negative control groups,and the AEG-1 gene knockout rates were 77.1％ and 79.8％,respectively,the differences were statistically significant (both at P＜0.01).There were no significant differences in the relative expression of AEG-1 mRNA between normal control groups and negative control groups (all at P＞0.05).Western blot showed that no significant changes were found in the AEG-1 proteins expression levels between normal control groups and negative control groups in the two kinds of cell lines (F=146.17,P＜0.01;F=156.79,P＜0.01).The expression levels of AEG-1 protein in the lentiviral infection groups were significantly lower than that in negative control groups (all at P＜0.01).The proliferation of both cells lines in lentiviral infection groups were significantly lower than that in negative control groups from the second day to the fifth day,the differences were statistically significant (t =5.78,30.68,23.99,29.40,all at P ＜ 0.01;t =7.88,7.09,5.56,6.60,all at P ＜ 0.01).In both cell lines,the apoptosis rate of lentiviral infection groups were significantly higher than those in the negative control groups,the differences were statistically significant (t =54.34,P＜0.01;t =11.68,P＜0.01).In both cell lines,the multiple of invasions in lentiviral infection groups were significantly lower than those in negative control groups,and the differences were statistically significant (t =16.04,P＜0.01;t =13.98,P＜0.01);In both cell lines,the multiple of transfer in lentiviral infection groups were significantly lower than those in negative control groups,and the differences were statistically significant (t =12.04,P ＜ 0.01;t =22.43,P ＜ 0.01).Conclusions Lentivirus transfection inducing knockdown of AEG-1 inhibits the transcription and protein expression level of AEG-1 in the melanoma cells,which changes the biological behaviors of UM,like slowing down cell proliferation,promoting apoptosis,and reducing the abilities of cells' invasion and metastasis.
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Objective To investigate the relationship between the expression of astrocyte elevated gene-1 (AEG-1) and its clinical pathological features in uveal melanoma.Methods Paraffm tissue specimens of 50 patients (50 eyes) with confirmed diagnosis of uveal melanoma (UM) were collected as experimental group,and samples from 11 patients (11 eyes) who underwent ocular excision due to trauma,still with largely intact uveal tissue,were selected as control group in the Department of Ophthalmology of Beijing Tongren Hospital from January 2013 to May 2017.Then the expression of AEG-1 in paraffm-embedded specimens was detected by immunohistochemical methods,and the correlation of AEG-1 expression with the clinical pathological data was analyzed.Results AEG-1 protein staining presented accurate pink or red granules,mainly located in UM nucleus,cytoplasm,cell membrane.In the experimental group,negative expression of AEG-1 was in 21 eyes (42.0％),and positive expression was in 29 eyes (58.0％),while AEG-1 were negatively expressed in the control group,and the difference in the two groups was statistically significant (P =0.000),suggesting that the expression of AEG-1 was upregulated in UM.In the experimental group,AEG-1 positive expression rate in patients with clinical pathological risk factors was significantly higher than that in patients without high risk factors (all P ＜ 0.05),and the positive expression rate of AEG-1 in UM with involvement of the ciliary body and iris neovascularization,the maximum diameter of tumor base ＞ 16 mm,tumor thickness ＞ 8 mm,tumor cell type belonging to mixed cell type and epithelioid/mixed cell type,and extra ocular tumor growth was 73.1％,73.9％,95.2％,82.4％,83.3％,74.1％ and 69.4％,respectively.However,there was no significant difference in AEG-1 expression among general clinical data including gender,eyes,age,optic disc involvement,secondary retinal detachment,epithelioid cell type and scleral duct invasion (all P ＞ 0.05).Conclusion AEG-1 is overexpressed in UM and has a significant correlation with multiple clinical risk factors,suggesting that high expression of AEG-1 may be one of the important prognostic indicators for UM.
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Objective To investigate the mechanism of miR-758 in hepatocellular carcinoma cell HepG2,and to investigate the regulatory role of miR-758 on astrocyte elevated gene-1 (AEG-1).Methods Transient transfection of miR-758 into HepG2 cells was performed to study the effect of miR-758 on tumor cell metastasis by transwell migration and invasion experiments.CCK8 assay was used to detect the cell proliferation activity.The cell cycle was analyzed by flow cytometry.The effect of miR-758 on epidermal mesenchymal transition (EMT) was determined by the expression of EMT markers.Transient transfection of miR-758 into human umbilical vein endothelial cells (HUVECs) was performed to explore the effect of miR-758 on luminal formation.AEG-1 3'UTR containing the binding site of miR-758 was constructed into luciferase expression vector.The miR-758 and the vector was co-transfected into HepG2 cells.And then the change in expression level of AEG-1 protein was detected through Western Blot.Results The overexpression of miR-758 inhibited HepG2 cell migration and invasion,as well as the cell proliferation and the cell cycle.The miR-758 was also found to inhibit EMT of HepG2 cells and the lumen formation of HUVEC cells.After the co-transfection of miR-758 with the plasmid containing AEG-1 gene 3'UTR into HepG2 cells,the luciferase expression was decreased.The luciferase expression was restored when the binding site of miR-758 in the 3'UTR was mutated.Further evidence by Western Blot showed the protein level of AEG-1 in HepG2 cells was significantly decreased after transfection of miR-758.Conclusions The miR-758 negatively regulates multiple steps during cancer metastasis,including cell migration,invasion,cell proliferation,EMT,as well as angiogenesis.And AEG-1 has been identified as a downstream target of miR-758.
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Objective To analyze the expressions of astrocyte elevated gene-1 (AEG-1 )and Beclin-1 (BECN-1 )in papillary thyroid carcinoma (PTC)and their clinical significances.Methods Thirty patients with PTC who were performed total thyroidectomy in the General Hospital Affiliated to Tianjin Medical University from October 201 5 to May 201 6 were collected.All patients were diagnosed with unilateral PTC.The tumor tissues were taken from the patients′ipsilateral thyroids,and 30 cases of normal tissues were taken from the patients′contralateral normal thyroids.The expressions of AEG-1 and BECN-1 in PTC tissues were detected by reverse transcription-poly-merase chain reaction (RT-PCR).The relationships between the expression status and clinicopathologic features were analyzed.Results The positive expression levels [M(QR )]of AEG-1 in PTC and the normal tissues were 0.626 1 (0.741 4)and 0.049 8 (0.01 1 8)respectively,with a significant difference (Z=-4.488,P=0.000). The positive expression levels of BECN-1 in PTC and the normal tissues were 0.067 9 (0.1 98 1 )and 0.785 7 (0.361 7)respectively,with a significant difference (Z=-5.441 ,P=0.000).In PTC,the expressions of AEG-1 and BECN-1 were related to TNMstaging (Z=-3.980,P=0.000;Z=-2.265,P=0.023)and lymphatic metas-tasis (Z=-3.1 90,P=0.001;Z=-2.640,P=0.008),but they were not related to age (Z=-1 .203,P=0.229;Z=-1 .1 62,P=0.245),gender (Z=-1 .222,P=0.222;Z=-0.453,P=0.651 )and tumor size (Z=-1 .496,P=0.1 35;Z=-1 .1 66,P=0.244).The expression of AEG-1 was negatively correlated with that of BECN-1 (r=-0.343,P=0.007).Conclusion The expression of AEG-1 in PTC is higher than that in normal tissues and the expression of BECN-1 in PTC is lower than that in normal tissues,and the expressions of AEG-1 and BECN-1 are related to TNM staging and lymphatic metastasis,which are expected to become prognostic indicators.
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ObjectiveTo investigate the expression and clinical significance of astrocyte elevated gene-1 (AEG-1), β-catenin, and cyclin D1 in hepatocellular carcinoma (HCC) tissues. MethodsA total of 40 HCC samples and 40 samples of corresponding para-carcinoma tissues from the patients with pathologically confirmed HCC who underwent surgery in The People′s Hospital of Guizhou from July 2013 to December 2014 were randomly selected, and 8 samples of normal liver tissues were selected as controls. The immunohistochemistry SP was used to measure the protein expression of AEG-1, β-catenin, and cyclin D1 in HCC tissues, corresponding para-carcinoma tissues, and normal liver tissues, and the correlation between their expression and HCC clinicopathological characteristics was analyzed. The chi-square test or Fisher′s exact test was used for comparison of categorical data between groups, and the Spearman rank correlation was used to analyze the correlation of AEG-1 with β-catenin, and cyclin D1 in HCC. ResultsHCC tissues and para-carcinoma tissues showed significantly higher protein expression of AEG-1, β-catenin, and cyclin D1 than normal liver tissues (χ2=7.840, 4.274, 8.817, 4.274, 9.919, and 4.850, P=0.005, 0.039, 0.003, 0.039, 0.002, and 0.028). The positive expression of AEG-1, β-catenin, and cyclin D1 showed no significant differences across the patients with different sexes, ages, HBsAg status, or tumor sizes (all P＞0.05), but showed significant differences across the patients with different degrees of pathological differentiation, TNM stages for liver cancer, and metastases (all P＜0.05). The correlation analysis showed that the protein expression of AEG-1 was positively correlated with that of β-catenin and cyclin D1 (r=0.420 and 0.741, both P＜0.01). ConclusionAEG-1, β-catenin, and cyclin D1 may play vital roles in the development and progression of HCC. AEG-1 may up-regulate the expression and activity of cyclin D1 and β-catenin and thus promote the development and metastasis of HCC. A combined measurement of AEG-1, β-catenin, and cyclin D1 can be used as an important parameter for HCC gene therapy and prognostic evaluation.
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Objective: To detect the expression level of astrocyte elevated gene-1 (AEG -1) in human bladder cancer cell lines, and to investigate the effects of down-regulation of AEG-1 expression on proliferation and invasion of bladder cancer T24 cells. Methods: The expression level of AEG-1 protein in normal bladder urinary epithelial cell line SV-HUC-1 and bladder cancer cell lines RT4, J82, 5637 and T24 was detected by Western blotting and immuno?uorescence staining. The recombinant virus with specific shRNA targeting AEG -1 gene was infected into bladder cancer T24 cells with high-expression of endogenous AEG-1. The stable infected clones were screened by puromycin, and the silencing efficiency of AEG -1 gene was confirmed by Western blotting. Then the effects of AEG -1 gene-silencing on the cell proliferation, migration and invasion were examined by CCK-8 method, wound healing assay and Transwell chamber assay, respectively. Results: The expression levels of AEG-1 in 4 bladder cancer cell lines were significantly higher than that in normal bladder urinary epithelial cell line (all P < 0.05). After infection AEG-1 shRNA with the recombinant virus carrying AEG-1 shRNA, the expression level of AEG-1 protein was effectively down-regulated in bladder cancer T24 cells (P < 0.05). As compared with the negative shRNA transfection group, the proliferation of T24 cells after AEG -1 genesilencing was obviously inhibited (P < 0.05), and the migration and invasion abilities of T24 cells after AEG -1 gene-silencing were significantly decreased (both P < 0.05). Conclusion: Silencing AEG -1 gene expression can inhibit the proliferation, migration and invasion of bladder cancer cells, which suggests that AEG-1 maybe paly a role in promoting the malignant biological behavior of bladder cancer cells.
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Objective To study the expressions of apoptotic protease activating factor-1(Apaf-1)and astrocyte elevated gene-1(AEG-1)in colonic carcinoma,and to explore their correlations with the clinical path-ological features. Methods The expressions of Apaf-1 and AEG-1 were detected in 63 colonic carcinoma sam-ples and 30 normal colonic mucosa adjacent to tumor nest by immunohistochemical method,and their correla-tions with clinical features of colonic carcinoma were analyzed. Results The positive expressions of Apaf-1 and AEG-1 in colonic carcinoma were 23. 81%(15 / 63)and 68. 25%(43 / 63),respectively. The positive expre-ssions of Apaf-1 and AEG-1 in normal colonic mucosa were 76. 67%(23 / 30)and 26. 67%(8 / 30),respec-tively. The positive expression rate of AEG-1 was significantly higher in colonic carcinoma than that in normal tissue(χ2 = 14. 192,P = 0. 000). However,the expression of Apaf-1 was signi-ficantly lower in colonic carci-noma than that in normal tissue(χ2 = 23. 497,P = 0. 000). The expression of Apaf-1 was negatively correlated to the expression of AEG-1(r = - 0. 339,P = 0. 007). The expressions of AEG-1 and Apaf-1 were associated with differentiation degree(χ2 = 4. 643,P = 0. 031;χ2 = 12. 034,P = 0. 001)and clinical stage(χ2 = 6. 628, P = 0. 010;χ2 = 8. 246,P = 0. 004),but they were not correlated with age(χ2 = 1. 462,P = 0. 227;χ2 =2. 401,P = 0. 121)and tumor size(χ2 = 0. 333,P = 0. 564;χ2 = 0. 590,P = 0. 442). Conclusion The expression of AEG-1 is up-regulated in colonic carcinoma,but the expression of Apaf-1 is down-regulated,with a significant negative correlation. Apaf-1 and AEG-1 may be closely related to the occurrence and development of colon carcinoma. Therefore,combination detection of Apaf-1 and AEG-1 may be more valuable for the prog-nosis evaluation of colonic carcinoma.
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Objective To investigate the expression of astrocyte elevated gene -1( AEG-1) and matrix metallopeptidase 9(MMP-9)in colorectal tissues and evaluate its correlation with clinical pathologic factors of colorectal cancer.Methods AEG-1 and MMP-9 expression in normal colorectal mucous (n=45),low-grade adenoma(n=31),high-grade adenoma(n=15)and colorectal carcinoma(n=146)were examined by immuno-histochemistry .Statistical analyses were applied to test the significance of its expression .Results AEG-1 ex-pression levels were gradually elevated in normal tissues ,low-grade adenoma ,high-grade adenoma and colorec-tal carcinoma respectively .Furthermore ,there was a similar trend for MMP -9from normal mucous to adenoma and carcinoma .Statistical analysis revealed that AEG -1 expression was markedly correlated with the UICC stage,T classification,N classification,M classification,and histological differentiation in the colorectal cancer pa-tients,but not with age,gender,tumor location and tumor size.In addition,AEG-1 expression was positively cor-related with the MMP-9 expression in colorectal cancer .Besides,those patients with high AEG-1 and MMP-9 levels had shorter survival time ( P<0 .05 ) .Conclusion AEG-1 may be involved in carcinogenesis and pro-gression of colorectal carcinoma and can be a novel prognostic biomarker in patients with colorectal carcinoma .
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OBJECTIVE@#To prove whether astrocyte elevated gene-1 (AEG-1) plays a role in high glucose-stimulated Rho kinase activation and epithelial-mesenchymal transition (EMT) in human renal tubular epithelial (HK-2) cells.@*METHODS@#The protein levels of AEG-1, alpha-smooth muscle actin, E-cadherin and MYPT1 were determined by Western blot.@*RESULTS@#AEG-1 protein level was upregulated in HK-2 cells stimulated with high glucose. AEG-1 siRNA downregulated Rho kinase protein expression and blocked high glucose-induced EMT.@*CONCLUSIONS@#Our results show that AEG-1 acts a key role in high glucose-induced activation of Rho kinase and EMT in HK-2 cells.
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Objective To construct anti-astrocyte elevated gene-1(AEG-1)single-chain variable antibody (V23)prokaryotic ex-pression vector,and to conduct the protein purification and immunological activity detection.Methods The Primer5 software was applied to design the primers aiming at the gene sequence of the antibody anti-AEG-1 single-chain variable region for constructing the prokaryotic expression plasmid of PRsetC/V23.After the enzyme digestion by the restriction enzyme Pst1 and correct DNA se-quencing,the prokaryotic expression plasmid was led to E.coli BL21 ,the prokaryotic expression engineering strain containing the V23 gene was constructed.After the induction with IPTG,the interest protein was purified by the magnetic beads with the HIS tag,and the content of interest protein was determined by the SDS-PAGE electrophoresis.Western blot and ELISA were adopted to detect the immune activity of the nti-AEG-1 single-chain variable region antibody.Results For the constructed prokaryotic expres-sion plasmid PRsetC/V23,the single enzyme digestion and sequencing analysis displayed that the constructed V23 gene was com-pletely consistent to the designing sequences.After IPTG induction,SDS-PAGE electrophoresis showed an apparent protein band at 31×103 ,the Western blot detection showed a specific AEG-1 response band at 80 ×103 ,the ELISA test showed the positive re-sults.Conclusion The PRsetC/V23 prokaryotic expression plasmid and the V23 prokaryotic expression engineering strain are suc-cessfully constructed,this engineering strain can express anti-AEG-1 single-chain variable region antibody protein,and the protein has good immune activity.
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Objective: To prove whether astrocyte elevated gene-1 (AEG-1) plays a role in high glucose-stimulated Rho kinase activation and epithelial-mesenchymal transition (EMT) in human renal tubular epithelial (HK-2) cells. Methods: The protein levels of AEG-1, alpha-smooth muscle actin, E-cadherin and MYPT1 were determined by Western blot. Results: AEG-1 protein level was upregulated in HK-2 cells stimulated with high glucose. AEG-1 siRNA downregulated Rho kinase protein expression and blocked high glucose-induced EMT. Conclusions: Our results show that AEG-1 acts a key role in high glucose-induced activation of Rho kinase and EMT in HK-2 cells.
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Objective To investigate the effect of siRNA-down-regulating astrocyte elevated gene-1(AEG-1)on the proliferation and apoptosis of cervical carcinoma cells.Methods The designed and synthesized AEG-1 siRNA was transfected to the cervical car-cinoma SiHa cells.The influence of AEG-1 siRNA on the expression of AEG-1 gene was detected by real-time fluorescent quantita-tive-polymerase chain reaction (RT-PCR);the inhibiting effect of AEG-1 siRNA on the proliferation of cervical cancer SiHa cells was detected by the MTT method;the influence of AEG-1 siRNA on apoptosis and cell cycle of the cervical cancer SiHa cellswas determined by the flow cytometry.Results Compared with the control group,AEG-1 siRNA transfecting human cervical cancer Si-Ha cells could evidently down-regulate the expression of AEG-1 gene with statistical difference (P<0.01);at the same time,the dwn-regulation of AEG-1 gene expression could significantly inhibit the proliferation of the cervical cancer SiHa cells (P<0.01), promote the apoptosis of SiHa cells (P<0.01)and arrest the cell cycle in G0/G1 phase.Conclusion AEG-1 siRNA can down-regulate the expression of AEG-1 gene in the cervical carcinoma SiHa cells,inhibit the proliferation of the cervical carcinoma SiHa cells and promote their apoptosis.
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Objective To investigate the expression of astrocyte elevated gene 1(AEG-1) in non-small cell lung cancer(NSCLC) and its clinicalpathological significance .Methods The expression of AEG-1 in NSCLC tissues and adjacent normal lung tissues was detected by RT-PCR and Western blot .The expression of AEG-1 in 87 NSCLC samples and 54 non-cancerous lung tissues was ex-amined with immunohistochemistry .Results RT-PCR and Western blot indicated that AEG-1 was more expressed in NSCLC tis-sues compared with adjacent normal lung tissues .The positive rate of AEG-1 in NSCLC tissues was 52 .9% ,which was significantly higher than that in non-cancerous lung tissues .The difference between the two groups was significant (P=0 .007) .Relevance was analyzed between the expression of AEG-1 and clinicalpathological characteristic .The expression of AEG-1 was positively correlated with T stage and N stage(P<0 .05) .Conclusion AEG-1 was specifically up-regulated in NSCLC tissues compared with non-can-cerous lung tissues ,suggesting that AEG-1 may play an important role in tumor development and progression ,and could be identi-fied as a biomarker for diagnosis of NSCLC .
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Astrocyte elevated gene 1 (AEG-l), an important oncogene, has been confirmed to play a crucial role in progression (invasion, metastasis, angiogenesis and chemoresistance, etc) of multiple cancers. Over the past decade, studies have shown that AEG-l is overexpressed in cancers involving almost all organs, including neuroblastoma, melanoma, HCC, breast, prostate cancer, etc. Moreover, AEG-l is associated with multiple pathways including PI3/Akt and nuclear factor-kappa;B; (NF-kappa;B;). This review mainly outlines the multiple regulating role of AEG-l in the development and progression of tumor and to discuss its role as a novel target for treatment of malignant tumors.
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BACKGROUND: The astrocyte elevated gene-1 (AEG-1) was cloned as a novel HIV-1 and tumor necrosis factor-alpha-induced transcript from primary human fetal astrocytes. It has been reported that the AEG-1 expression is elevated in subsets of breast cancer, glioblastoma multiforme and melanoma cells, and AEG-1 cooperates with Ha-ras to promote the transformation of immortalized melanocytes. AEG-1 is thought to play a role in promoting cancer development and/or its maintenance. OBJECTIVE: The aim of this study is to determine whether AEG-1 is related to the pathogenesis of melanoma and other melanocytic lesions. METHODS: The nine biopsy specimens each of melanoma, dysplastic nevus, Spitz nevus and compound nevus were studied using immunohistochemical staining. The expressions of AEG-1 were evaluated using an immunostaining-intensity-distribution index. RESULTS: The expression of AEG-1 was significantly higher in the melanoma and dysplastic nevus than in the compound nevus. The expression was also significantly higher in the melanoma than in the Spitz nevus. CONCLUSION: AEG-1 may be related to the pathogenesis of both dysplastic nevus and melanoma, but it may not be related to Spitz nevus.
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Humans , Astrocytes , Biopsy , Breast Neoplasms , Clone Cells , Dysplastic Nevus Syndrome , Glioblastoma , HIV-1 , Melanocytes , Melanoma , Necrosis , Nevus , Nevus, Epithelioid and Spindle CellABSTRACT
BACKGROUND: The astrocyte elevated gene-1 (AEG-1) was cloned as a novel HIV-1 and tumor necrosis factor-alpha-induced transcript from primary human fetal astrocytes. It has been reported that the AEG-1 expression is elevated in subsets of breast cancer, glioblastoma multiforme and melanoma cells, and AEG-1 cooperates with Ha-ras to promote the transformation of immortalized melanocytes. AEG-1 is thought to play a role in promoting cancer development and/or its maintenance. OBJECTIVE: The aim of this study is to determine whether AEG-1 is related to the pathogenesis of melanoma and other melanocytic lesions. METHODS: The nine biopsy specimens each of melanoma, dysplastic nevus, Spitz nevus and compound nevus were studied using immunohistochemical staining. The expressions of AEG-1 were evaluated using an immunostaining-intensity-distribution index. RESULTS: The expression of AEG-1 was significantly higher in the melanoma and dysplastic nevus than in the compound nevus. The expression was also significantly higher in the melanoma than in the Spitz nevus. CONCLUSION: AEG-1 may be related to the pathogenesis of both dysplastic nevus and melanoma, but it may not be related to Spitz nevus.
Subject(s)
Humans , Astrocytes , Biopsy , Breast Neoplasms , Clone Cells , Dysplastic Nevus Syndrome , Glioblastoma , HIV-1 , Melanocytes , Melanoma , Necrosis , Nevus , Nevus, Epithelioid and Spindle CellABSTRACT
Astrocyte elevated gene-1 (AEG-1) was cloned as an human immunodeficiency virus -1-inducible and tumor necrosis factor-α-inducible transcript in primary human fetal astrocytes by a rapid subtraction hybridization approach. AEG-1 down-regulates the expression of the glutamate transporter EAAT2, thus, it is implicated in glutamate-induced excitotoxic damage to neurons as evident in HIV-associated neurodegeneration. Meanwhile, AEG-1 expression is elevated in subsets of breast cancer, prostatic cancer, glioblastoma multiforme and melanoma cells, having a dual specificity phosphatase activity. Overexpression of AEG-1 increases and siRNA inhibition of AEG-1 decreases migration and invasion of human glioma cells, respectively. Recent observations indicate that AEG-1 exerts its effects by activating the nuclear factor kappa B (NF-κB) pathway and AEG-1 is a downstream target of Ha-ras and plays an important role in Ha-ras-mediated tumorigenesis. These findings are intensifying interest in AEG-1 as a crucial regulator of tumor progression and metastasis and as a potential mediator of neurodegeneration.