Disease relevance of MAGEA1

• These distinctive epigenetic phenotypes of MAGEA1 and MAGEA3 also were observed in pure seminomas and in the seminomatous elements of mixed-type TGCTs [1].
• However, the MAGEA1 gene that was inactivated and hypermethylated in non-astrocytoma tissues, was partially demethylated in 24.5% of the astrocytoma tissues (co-existence of the hypermethylated and demethylated alleles) [2].
• It is expressed in a larger proportion of melanoma samples than MAGE-1 [3].
• Sixteen of 100 primary tumors vs. 69 (48%) of 145 metastases from individual patients expressed MAGE-1 [4].
• Expression of MAGE genes in transitional-cell carcinomas of the urinary bladder [5].

Psychiatry related information on MAGEA1

• The sample was derived from the Kungsholmen Project in Stockholm, Sweden, and consisted of (n = 85) healthy older adults (M age = 81.80 years; M MMSE = 28.34) and (n = 21) diagnosed Alzheimer's Disease (AD) patients (Mage = 81.80 years; M MMSE = 23.55) [6].
• Participants included 39 individuals (Mage = 25.86; 69% female) with a primary diagnosis of panic disorder (with and without agoraphobia) recruited through the general community [7].
• A downward extension of a Dutch version of Harter's Self-Perception Profile for Children (SPPC) was tested in a Flemish sample of 880 1st to 3rd graders (Mage = 7.18 years, SD = 0.80) [8].

High impact information on MAGEA1

• A gene family named MAGE codes for antigens recognized by autologous CTL on a melanoma tumor [9].
• Some of them are encoded by genes MAGE-1 and MAGE-3, which are not expressed in normal tissues except in testis [10].
• Like the MAGE genes, it is silent in normal tissues with the exception of testis [10].
• The immunological mechanism, as shown for GM-CSF-transduced DCs, involves MAGE-1-specific CD4(+) and CD8(+) T cells [11].
• MAGE-type genes are expressed by many tumors of different histological types and not by normal cells, except for male germline cells, which do not express major histocompatibility complex (MHC) molecules [12].

Chemical compound and disease context of MAGEA1

• To determine if uveal melanoma patients would be suitable for MAGE-peptide immunotherapy, the expression of MAGE-1, -2, -3 and -4 genes was assessed by reverse transcription followed by polymerase chain reaction (RT-PCR) amplification and ethidium bromide staining [13].
• Forty-three germ cell tumors (24 seminomas, six embryonal carcinomas and 13 mixed germ cell tumors), and 10 Leydig cell tumors were selected for study, and standard immunohistochemical techniques were used on formalin-fixed paraffin-embedded tissues using mouse monoclonal antibodies to MAGE-1 (clone M454) and MAGE-3 (clone 57B) antigens [14].
• We previously reported some cancer testis antigens, especially for MAGE genes, to be expressed in a relatively high population of gastro-intestinal and breast cancers [15].
• An additional apparent consequence of global hypomethylation is reactivation of the cancer-testis antigen MAGEA1 via promoter demethylation, but only in GBMs and GBM cell lines exhibiting a 5-methylcytosine content below a threshold of approximately 50% [16].
• The induction of MAGE-1, -2, -3, and -4 gene expression in eight colorectal carcinoma cell lines also was examined by use of a demethylating agent, 5-Aza-2'-deoxycytidine (DAC) [17].

Biological context of MAGEA1

• Like MAGE-1, MAGE-3 is composed of three exons and the large open reading frame is entirely located in the third exon [3].
• To investigate the interaction of the HLA-A1-restricted MAGE-1 peptide 161-169 (EADPT-GHSY) with HLA class I molecules, photoreactive derivatives were prepared by single amino acid substitution with N beta-[iodo-4-azidosalicyloyl]-L-2,3-diaminopropionic acid [18].
• The predicted amino acid sequences of MAGE-X2 and MAGE-3b contain consensus HLA-A1 peptide binding motifs, suggesting that, like MAGE-1, they may code for tumor-associated antigens [19].
• Owing to the high incidence of MAGE gene expression in esophageal squamous-cell carcinoma, a large proportion of patients could be suitable candidates for immune therapies involving tumor-specific antigens encoded by MAGE genes [20].
• BACKGROUND & AIMS: The genes MAGE-1 and MAGE-3 both encode melanoma peptide antigens recognized by major histocompatibility complex-restricted cytotoxic T lymphocytes [21].

Anatomical context of MAGEA1

• Identification of a promiscuous T-cell epitope encoded by multiple members of the MAGE family [22].
• Consistent with the notion that the peptide encoded by MAGE-1 codons 127-136 is, indeed, processed from the proteins encoded by all four MAGE family members, the CTLs were able to specifically recognize Cos-7 cells cotransfected with HLA-B*3701 and any of these MAGE genes [22].
• By flow cytometry, we show that mage-1 protein is expressed within myeloma cells and cell lines and that anti-mage-1.HLA-A1 cytotoxic T lymphocytes efficiently killed MAGE-1+HLA-A1+ MDN myeloma cells [23].
• These antigens may constitute useful targets for anti-cancer immunotherapy, since no expression of MAGE genes has been observed in normal tissues other than testis [5].
• MAGE-1 and MAGE-3 tumor rejection antigens in human germ cell tumors [14].

Associations of MAGEA1 with chemical compounds

• Competition experiments using single Ala-substituted peptides indicated that amino acid residues Asp in position 3 and Tyr in position 9 were essential for binding of the MAGE-1 peptide to HLA-A1 [3].
• Finally, the HLA-B44 photoaffinity labeling, unlike the HLA-A1 and HLA-A29 labeling, was inhibited more efficiently by the corresponding MAGE decapeptides, which is consistent with the reported HLA-B44 peptide-binding motif (glutamic acid in P2, and C-terminal tyrosine or phenylalanine) [18].
• Overexpression of MAGE/GAGE genes in paclitaxel/doxorubicin-resistant human cancer cell lines [24].
• To estimate the possibility of activating the MAGE-A1 gene with demethylating agents with a view toward clinical use, we assessed the methylation status of its CpG-rich promoter by sodium bisulfite mapping both of samples that express the gene and those that do not [25].
• Finally, treatment of MAGE-1-mRNA-negative cell lines with 5-Aza-2'-deoxycytidine, a hypomethylating agent known to induce MAGE-1 expression, resulted in the expression of the 72-kDa protein [26].

Physical interactions of MAGEA1

• MAGE peptide binding by HLA-A29 and HLA-B44 was confirmed by photoaffinity labeling with photoreactive MAGE-3 peptide derivatives on C1R.A29 and C1R.B44 cells, respectively [18].
• An immunoassay was developed in which ME491 was absorbed to polystyrene beads in order to bind the melanoma-associated antigen present in serum [27].

Regulatory relationships of MAGEA1

• All but one of the tumors expressing MAGE-1 also expressed MAGE-3 [5].
• METHODS: Total cellular mRNA was extracted from six melanoma biopsies, reverse-transcribed and tested in 25-45 cycles of reverse polymerase chain reaction (rtPCR) in the presence of primers' pairs specific for the beta-actin-positive control gene and for the MAGE-1-encoding gene [28].
• The members of MAGE gene family are highly expressed in human hepatocellular carcinoma (HCC) [29].
• A novel IFN-gamma regulated human melanoma associated antigen gp33-38 defined by monoclonal antibody Me14/D12. I. Identification and immunochemical characterization [30].

Other interactions of MAGEA1

• The antigenic peptide of MZ2-D is a nonapeptide that is encoded by the sequence of MAGE-3 that is homologous to the MAGE-1 sequence coding for the MZ2-E peptide [3].
• In line with observations made with gene MAGE-1 (HGMW-approved symbol MAGE1), we found that promoter 1.5 stimulated a high level of transcription in a melanoma cell line that does not express MAGE-4 [31].
• The spectrum of MAGE gene expression in the human melanoma cell line DM150 was examined using reverse transcription polymerase chain reaction and cDNA cloning [19].
• Identification of potential CTL epitopes of tumor-associated antigen MAGE-1 for five common HLA-A alleles [32].
• RT-PCR for detection of BAGE, GAGE, and MAGE gene expression was positive in two adenomas and nine carcinomas, but negative in normal salivary gland tissue [33].

Analytical, diagnostic and therapeutic context of MAGEA1

• The overlapping binding of homologous MAGE peptides by HLA-A1, A29, and B44 is based on different binding principles and may have implications for immunotherapy of MAGE-positive tumors [18].
• MAGE-1 and MAGE-3 represent targets for specific immunotherapy because they encode peptide antigens which are recognised by cytotoxic T lymphocytes (CTL) when presented by HLA class I molecules, and pilot clinical trials with these peptides are currently in progress [13].
• We have determined whether esophageal carcinoma patients should be eligible for MAGE-peptide-based vaccine therapies [20].
• Thus, precisely targeted immunotherapy directed against antigen MZ2-E could be provided to individuals identified by HLA typing and analysis of the RNA of a small tumor sample [34].
• All three rabbit anti-peptide antisera showed reactivity against the immunizing peptide, and one reacted with the recombinant MAGE-1 protein by immunoblotting, but none reacted with cell lysates from MAGE-1 mRNA-positive cells [35].

References