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Gene Review

MAGEA3  -  melanoma antigen family A, 3

Homo sapiens

Synonyms: Antigen MZ2-D, CT1.3, Cancer/testis antigen 1.3, HIP8, HYPD, ...
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Disease relevance of MAGEA3


High impact information on MAGEA3

  • Some of them are encoded by genes MAGE-1 and MAGE-3, which are not expressed in normal tissues except in testis [4].
  • In a patient vaccinated with a MAGE-3 antigen presented by HLA-A1, we measured the frequencies of anti-vaccine and antitumor T cells in several metastases to evaluate their respective potential contribution to tumor rejection [5].
  • These Th1 cells recognized not only peptides, but also DCs loaded with Mage-3 protein, and in case of Mage-3DP4-specific Th1 cells IFN-gamma was released even after direct recognition of viable, Mage-3-expressing HLA-DP4+ melanoma cells [6].
  • By stimulating human CD8(+) T lymphocytes with autologous dendritic cells infected with an adenovirus encoding MAGE-3, we obtained a cytotoxic T lymphocyte (CTL) clone that recognized a new MAGE-3 antigenic peptide, AELVHFLLL, which is presented by HLA-B40 [7].
  • Since this treatment is known to induce the exchange of the three catalytic subunits of the proteasome to form the immunoproteasome, this result suggested that the processing of this MAGE-3 peptide required the immunoproteasome [7].

Chemical compound and disease context of MAGEA3

  • 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 [8].
  • Finally, 5-aza-2'-deoxycytidine induced a 16-fold increase of MAGE3 expression in Mel 313 melanoma cells expressing constitutively low levels of the antigen, but did not affect that of Mel 275 melanoma cells expressing high baseline levels of MAGE3 [9].
  • Furthermore, de novo expression of MAGE3 gene induced by the treatment of Mel 195 melanoma cells with the DNA hypomethylating agent 5-aza-2'-deoxycytidine was associated with a 6%-12% demethylation of selected cytosine-guanine dinucleotides in its promoter [9].
  • CONCLUSION: The prognostic value of this method could be improved by combining it with PCR of other melanoma markers (Melan A, Mage 3) or assays of serum markers (S 100 protein or lactate dehydrogenase) [10].
  • Furthermore, treatment of melanoma cells expressing the MAGE-3 protein with lactacystin resulted in efficient lysis by MAGE-3271-279-specific CTL [11].

Biological context of MAGEA3


Anatomical context of MAGEA3


Associations of MAGEA3 with chemical compounds

  • Either MAGE-1 or -3 gene expressions were induced in 1 of 3 MAGE-1 negative breast cell lines or 1 of 3 MAGE-3 negative breast cell lines by the treatment with 5-aza-2'-deoxycytidine [16].
  • Specifically, the MAGE-3 gene was linked to a leader sequence at its NH2 terminus for secretion and to a cell-binding domain at its COOH terminus for receptor-mediated internalization [17].
  • CONCLUSIONS: Sequential DAC/DP treatment may be a novel strategy to simultaneously augment MAGE-3 expression and induce growth arrest in thoracic malignancies [18].
  • Similar stability data were also obtained for MAGE-3, another N-terminal glutamic acid containing CTL peptide in clinical development, leading us to suggest that all N-terminal glutamic acid and probably glutamine-containing CTL peptide epitopes may be stabilized as hydrochloride salts [19].

Physical interactions of MAGEA3

  • 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 [20].
  • RESULTS: Using native CLL cells as antigen-presenting cells (APCs), we demonstrate the generation of MDM2-specific T cells in 7/12 CLL patients that recognized specifically the MDM2-derived peptide MDM2(81-88) bound to HLA-A2-dimers while they were inactive against an unrelated MAGE-3 peptide (p = 0.002) [21].

Regulatory relationships of MAGEA3


Other interactions of MAGEA3

  • 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].
  • Higher homology was found between MAGE-3 and -6 (98% at the nt level) and also between MAGE-4 and -41 (98%) [25].
  • Finally, we demonstrate that brain metastasis-derived cell cultures significantly overexpress Melan-A and MAGE-3, compared to primary tumours and other metastatic sites (P-value range: 0.05-0.001) [26].
  • In contrast, photoaffinity labeling of HLA-A29 was efficiently inhibited by these as well as by the MAGE-3 and MAGE-6 nonapeptides [20].
  • Among 46 primary lung cancers, high expression rates were found for MAGE-3 (41%, 19/46), and SSX-4 (35%, 16/46) [27].

Analytical, diagnostic and therapeutic context of MAGEA3


  1. Distinctive epigenetic phenotype of cancer testis antigen genes among seminomatous and nonseminomatous testicular germ-cell tumors. Zhang, C., Kawakami, T., Okada, Y., Okamoto, K. Genes Chromosomes Cancer (2005) [Pubmed]
  2. The clinical significance of MAGEA3 expression in pancreatic cancer. Kim, J., Reber, H.A., Hines, O.J., Kazanjian, K.K., Tran, A., Ye, X., Amersi, F.F., Martinez, S.R., Dry, S.M., Bilchik, A.J., Hoon, D.S. Int. J. Cancer (2006) [Pubmed]
  3. Human gene MAGE-3 codes for an antigen recognized on a melanoma by autologous cytolytic T lymphocytes. Gaugler, B., Van den Eynde, B., van der Bruggen, P., Romero, P., Gaforio, J.J., De Plaen, E., Lethé, B., Brasseur, F., Boon, T. J. Exp. Med. (1994) [Pubmed]
  4. BAGE: a new gene encoding an antigen recognized on human melanomas by cytolytic T lymphocytes. Boël, P., Wildmann, C., Sensi, M.L., Brasseur, R., Renauld, J.C., Coulie, P., Boon, T., van der Bruggen, P. Immunity (1995) [Pubmed]
  5. Contrasting frequencies of antitumor and anti-vaccine T cells in metastases of a melanoma patient vaccinated with a MAGE tumor antigen. Lurquin, C., Lethé, B., De Plaen, E., Corbière, V., Théate, I., van Baren, N., Coulie, P.G., Boon, T. J. Exp. Med. (2005) [Pubmed]
  6. Rapid induction of tumor-specific type 1 T helper cells in metastatic melanoma patients by vaccination with mature, cryopreserved, peptide-loaded monocyte-derived dendritic cells. Schuler-Thurner, B., Schultz, E.S., Berger, T.G., Weinlich, G., Ebner, S., Woerl, P., Bender, A., Feuerstein, B., Fritsch, P.O., Romani, N., Schuler, G. J. Exp. Med. (2002) [Pubmed]
  7. The production of a new MAGE-3 peptide presented to cytolytic T lymphocytes by HLA-B40 requires the immunoproteasome. Schultz, E.S., Chapiro, J., Lurquin, C., Claverol, S., Burlet-Schiltz, O., Warnier, G., Russo, V., Morel, S., Lévy, F., Boon, T., Van den Eynde, B.J., van der Bruggen, P. J. Exp. Med. (2002) [Pubmed]
  8. MAGE-1 and MAGE-3 tumor rejection antigens in human germ cell tumors. Cheville, J.C., Roche, P.C. Mod. Pathol. (1999) [Pubmed]
  9. Promoter methylation controls the expression of MAGE2, 3 and 4 genes in human cutaneous melanoma. Sigalotti, L., Coral, S., Nardi, G., Spessotto, A., Cortini, E., Cattarossi, I., Colizzi, F., Altomonte, M., Maio, M. J. Immunother. (2002) [Pubmed]
  10. Prognostic value of tyrosinase reverse-transcriptase polymerase chain reaction in metastatic melanoma. Quereux, G., Denis, M., Khammari, A., Lustenberger, P., Dreno, B. Dermatology (Basel) (2001) [Pubmed]
  11. Modulation of proteasomal activity required for the generation of a cytotoxic T lymphocyte-defined peptide derived from the tumor antigen MAGE-3. Valmori, D., Gileadi, U., Servis, C., Dunbar, P.R., Cerottini, J.C., Romero, P., Cerundolo, V., Lévy, F. J. Exp. Med. (1999) [Pubmed]
  12. Cancer-testis antigens are commonly expressed in multiple myeloma and induce systemic immunity following allogeneic stem cell transplantation. Atanackovic, D., Arfsten, J., Cao, Y., Gnjatic, S., Schnieders, F., Bartels, K., Schilling, G., Faltz, C., Wolschke, C., Dierlamm, J., Ritter, G., Eiermann, T., Hossfeld, D.K., Zander, A.R., Jungbluth, A.A., Old, L.J., Bokemeyer, C., Kröger, N. Blood (2007) [Pubmed]
  13. The expression of tumor-rejection antigen "MAGE" genes in human gastric carcinoma. Inoue, H., Mori, M., Honda, M., Li, J., Shibuta, K., Mimori, K., Ueo, H., Akiyoshi, T. Gastroenterology (1995) [Pubmed]
  14. Analysis of MAGE-3-specific cytolytic T lymphocytes in human leukocyte antigen-A2 melanoma patients. Valmori, D., Liénard, D., Waanders, G., Rimoldi, D., Cerottini, J.C., Romero, P. Cancer Res. (1997) [Pubmed]
  15. The cancer germ-line genes MAGE-1, MAGE-3 and PRAME are commonly expressed by human myeloma cells. Pellat-Deceunynck, C., Mellerin, M.P., Labarrière, N., Jego, G., Moreau-Aubry, A., Harousseau, J.L., Jotereau, F., Bataille, R. Eur. J. Immunol. (2000) [Pubmed]
  16. Expression of MAGE and BAGE genes in Japanese breast cancers. Fujie, T., Mori, M., Ueo, H., Sugimachi, K., Akiyoshi, T. Ann. Oncol. (1997) [Pubmed]
  17. A retrogen strategy for presentation of an intracellular tumor antigen as an exogenous antigen by dendritic cells induces potent antitumor T helper and CTL responses. You, Z., Hester, J., Rollins, L., Spagnoli, G.C., van der Bruggen, P., Chen, S.Y. Cancer Res. (2001) [Pubmed]
  18. Induction of MAGE-3 expression in lung and esophageal cancer cells. Weiser, T.S., Ohnmacht, G.A., Guo, Z.S., Fischette, M.R., Chen, G.A., Hong, J.A., Nguyen, D.M., Schrump, D.S. Ann. Thorac. Surg. (2001) [Pubmed]
  19. Stability and CTL activity of N-terminal glutamic acid containing peptides. Beck, A., Bussat, M.C., Klinguer-Hamour, C., Goetsch, L., Aubry, J.P., Champion, T., Julien, E., Haeuw, J.F., Bonnefoy, J.Y., Corvaia, N. J. Pept. Res. (2001) [Pubmed]
  20. HLA photoaffinity labeling reveals overlapping binding of homologous melanoma-associated gene peptides by HLA-A1, HLA-A29, and HLA-B44. Luescher, I.F., Romero, P., Kuznetsov, D., Rimoldi, D., Coulie, P., Cerottini, J.C., Jongeneel, C.V. J. Biol. Chem. (1996) [Pubmed]
  21. MDM2 is recognized as a tumor-associated antigen in chronic lymphocytic leukemia by CD8+ autologous T lymphocytes. Mayr, C., Bund, D., Schlee, M., Bamberger, M., Kofler, D.M., Hallek, M., Wendtner, C.M. Exp. Hematol. (2006) [Pubmed]
  22. Expression of MAGE genes in transitional-cell carcinomas of the urinary bladder. Patard, J.J., Brasseur, F., Gil-Diez, S., Radvanyi, F., Marchand, M., François, P., Abi-Aad, A., Van Cangh, P., Abbou, C.C., Chopin, D. Int. J. Cancer (1995) [Pubmed]
  23. Dendritic cells containing apoptotic melanoma cells prime human CD8+ T cells for efficient tumor cell lysis. Jenne, L., Arrighi, J.F., Jonuleit, H., Saurat, J.H., Hauser, C. Cancer Res. (2000) [Pubmed]
  24. Generation of specific antitumor reactivity by the stimulation of spleen cells from gastric cancer patients with MAGE-3 synthetic peptide. Fujie, T., Tanaka, F., Tahara, K., Li, J., Tanaka, S., Mori, M., Ueo, H., Takesako, K., Akiyoshi, T. Cancer Immunol. Immunother. (1999) [Pubmed]
  25. Sequence analysis of the MAGE gene family encoding human tumor-rejection antigens. Imai, Y., Shichijo, S., Yamada, A., Katayama, T., Yano, H., Itoh, K. Gene (1995) [Pubmed]
  26. Expression of melanoma-associated antigens in melanoma cell cultures. Urosevic, M., Braun, B., Willers, J., Burg, G., Dummer, R. Exp. Dermatol. (2005) [Pubmed]
  27. Expression of cancer/testis (CT) antigens in lung cancer. Tajima, K., Obata, Y., Tamaki, H., Yoshida, M., Chen, Y.T., Scanlan, M.J., Old, L.J., Kuwano, H., Takahashi, T., Takahashi, T., Mitsudomi, T. Lung Cancer (2003) [Pubmed]
  28. Infrequent expression of the MAGE gene family in uveal melanomas. Mulcahy, K.A., Rimoldi, D., Brasseur, F., Rodgers, S., Liénard, D., Marchand, M., Rennie, I.G., Murray, A.K., McIntyre, C.A., Platts, K.E., Leyvraz, S., Boon, T., Rees, R.C. Int. J. Cancer (1996) [Pubmed]
  29. Expression of the MAGE gene family in human hepatocellular carcinoma. Tahara, K., Mori, M., Sadanaga, N., Sakamoto, Y., Kitano, S., Makuuchi, M. Cancer (1999) [Pubmed]
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