Biology:MAGEA3
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Melanoma-associated antigen 3 (MAGE-A3) is a protein that in humans is encoded by the MAGEA3 gene.[1][2][3]
Genetics
This gene is a member of the melanoma-associated antigen gene family. The members of this family encode proteins with 50 to 80% sequence identity to each other. The promoters and first exons of the MAGEA genes show considerable variability, suggesting that the existence of this gene family enables the same function to be expressed under different transcriptional controls. The MAGEA genes are clustered at chromosomal location Xq28. They have been implicated in some hereditary disorders, such as dyskeratosis congenita.[3]
Function and Clinical relevance
The normal function of MAGE-A3 in healthy cells is unknown.[4] The presence of the antigen on tumor cells has been associated with worse prognosis. In one study, high levels of MAGE-A3 in lung adenocarcinoma were associated with shorter survival.[5]
MAGE-A3 is a tumor-specific protein, and has been identified on many tumors including melanoma, non-small cell lung cancer, hematologic malignancies, among others.[6] Currently, GlaxoSmithKline is developing a cancer vaccine targeting MAGE-A3. The vaccine is a fusion protein of MAGE-A3 and Haemophilus influenzae protein D, combined with a proprietary immunoadjuvant.[7]
References
- ↑ "A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma". Science 254 (5038): 1643–7. Jan 1992. doi:10.1126/science.1840703. PMID 1840703.
- ↑ "The melanoma antigen gene (MAGE) family is clustered in the chromosomal band Xq28". Genomics 29 (3): 725–31. Mar 1996. doi:10.1006/geno.1995.9945. PMID 8575766.
- ↑ 3.0 3.1 "Entrez Gene: MAGEA3 melanoma antigen family A, 3". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4102.
- ↑ "Vaccination therapy for non-small-cell lung cancer: review of agents in phase III development". Annals of Oncology 23 (6): 1387–1393. Dec 2011. doi:10.1093/annonc/mdr564. PMID 22156658.
- ↑ Ali O. Gure; Ramon Chua; Barbara Williamson; Mithat Gonen; Cathy A. Ferrera; Sacha Gnjatic; Gerd Ritter; Andrew J.G. Simpson et al. (Nov 2005). "Cancer-Testis Genes Are Coordinately Expressed and Are Markers of Poor Outcome in Non–Small Cell Lung Cancer". Clinical Cancer Research 11 (22): 8055–8062. doi:10.1158/1078-0432.CCR-05-1203. PMID 16299236.
- ↑ Corporate Comms. "New data on MAGE-A3 cancer immunotherapy support potential novel options of treating non-small cell lung cancer and melanoma". Us.gsk.com. http://us.gsk.com/html/media-news/pressreleases/2008/2008_us_pressrelease_10076.htm.
- ↑ "Patent US20100008980 - Use of MAGE A3-Protein D Fusion Antigen in Immunotherapy Combined with ... - Google Patents". 2008-01-08. http://www.google.com/patents/US20100008980.
Further reading
- "Expression of MAGE genes in primary and metastatic cutaneous melanoma". Int. J. Cancer 63 (3): 375–80. 1995. doi:10.1002/ijc.2910630313. PMID 7591235.
- "Identification and intracellular location of MAGE-3 gene product". Cancer Res. 55 (11): 2236–9. 1995. PMID 7757970.
- "Structure, chromosomal localization, and expression of 12 genes of the MAGE family". Immunogenetics 40 (5): 360–9. 1994. doi:10.1007/BF01246677. PMID 7927540.
- "Cloning and analysis of MAGE-1-related genes". Biochem. Biophys. Res. Commun. 202 (1): 549–55. 1994. doi:10.1006/bbrc.1994.1963. PMID 8037761. https://zenodo.org/record/1229420.
- "Human gene MAGE-3 codes for an antigen recognized on a melanoma by autologous cytolytic T lymphocytes". J. Exp. Med. 179 (3): 921–30. 1994. doi:10.1084/jem.179.3.921. PMID 8113684.
- "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- "Analysis of MAGE-3-specific cytolytic T lymphocytes in human leukocyte antigen-A2 melanoma patients". Cancer Res. 57 (4): 735–41. 1997. PMID 9044853.
- "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. 1997. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- "Comparative Genome Sequence Analysis of the Bpa/Str Region in Mouse and Man". Genome Res. 10 (6): 758–75. 2000. doi:10.1101/gr.10.6.758. PMID 10854409.
- "Activation of melanoma antigen tumor antigens occurs early in lung carcinogenesis". Cancer Res. 61 (21): 7959–63. 2001. PMID 11691819.
- "Identification of immunodominant regions among promiscuous HLA-DR-restricted CD4+ T-cell epitopes on the tumor antigen MAGE-3". Blood 101 (3): 1038–44. 2003. doi:10.1182/blood-2002-03-0933. PMID 12393675.
- "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. 2003. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- "Detection of multiple melanoma-associated markers in melanoma cell lines by RT in situ PCR". Exp. Mol. Pathol. 74 (2): 140–7. 2003. doi:10.1016/S0014-4800(03)00012-1. PMID 12710945.
- "Ex vivo characterization of tumor-derived melanoma antigen encoding gene-specific CD8+cells in patients with hepatocellular carcinoma". J. Hepatol. 40 (1): 102–9. 2004. doi:10.1016/S0168-8278(03)00484-7. PMID 14672620.
- "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. 2004. doi:10.1101/gr.2596504. PMID 15489334.
- "Identification of two naturally presented MAGE antigenic peptides from a patient with hepatocellular carcinoma by mass spectrometry". Immunol. Lett. 99 (1): 113–21. 2005. doi:10.1016/j.imlet.2005.02.007. PMID 15885805.
- "Immunohistochemical expression of tumor antigens MAGE-A1, MAGE-A3/4, and NY-ESO-1 in cancerous and benign prostatic tissue". Prostate 66 (1): 13–8. 2006. doi:10.1002/pros.20312. PMID 16114059.
- "A newly identified MAGE-3-derived, HLA-A24-restricted peptide is naturally processed and presented as a CTL epitope on MAGE-3-expressing gastrointestinal cancer cells". Oncology 70 (1): 54–62. 2006. doi:10.1159/000091185. PMID 16446550.
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