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Gene Review:

MAGEA4 - melanoma antigen family A, 4

Homo sapiens

Synonyms: CT1.4, Cancer/testis antigen 1.4, MAGE-4 antigen, MAGE-41, MAGE-41 antigen, ...

Tsuzurahara, S. et al., Shichijo, S. et al., De Plaen, E. et al., Kobayashi, T. et al., Yutani, S. et al., et al.

Prasad, Jungbluth, Patel, Iversen, Hoshaw-Woodard, Busam,

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Disease relevance of MAGEA4

Various regions of the promoter of the fifth alternative exon (1.5) were cloned in a luciferase reporter plasmid, and the constructs were transfected in a sarcoma cell line that expresses MAGE-4 [1].
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 [1].
The present study was designed to determine whether elevated serum MAGE-4 protein levels can predict hepatocellular carcinogenesis in patients with liver cirrhosis before clinical diagnosis [2].
Gene MAGE-4, which is expressed in more than 50% of carcinomas of esophagus, head and neck, lung, and bladder, has two known alleles [3].
Detection of MAGE-4 protein in lung cancers [4].

High impact information on MAGEA4

Identification of MAGE-1 and MAGE-4 proteins in spermatogonia and primary spermatocytes of testis [5].
Here we show that 2B4 also binds to MAGE-4, a cancer testis antigen expressed in a variety of tumour cells, including breast carcinoma, seminoma and EBV-negative cases of Hodgkin's lymphoma [6].
Detection of MAGE-4 protein in sera of patients with head-and-neck squamous-cell carcinoma [7].
Similar differences in the frequency of gene expression between primary and metastatic tumor samples were observed for MAGE-2, MAGE-3, and MAGE-4 [8].
Expression of genes of the MAGE family, which encode tumor-rejection antigens recognized on HLA-AI and -Cw1601 by cytotoxic T lymphocytes (CTL), was investigated in lung cancers at the mRNA [MAGE-1, -2, -3/-6, and -4 (4a and/or 4b)] and protein (MAGE-4) levels [4].

Chemical compound and disease context of MAGEA4

MAGE-4 protein was positive in 21/45 (46.7%) HCC-C patients and 18/55 (32.7%) LC-C patients (cut-off, mean plus 2 SD in healthy controls) but in 0/12 (0%) hepatitis B virus-associated HCC (HCC-B) patients, 3/49 (6.1%) hepatitis B virus-associated LC (LC-B) patients, 4/47 (8.5%) alcoholic liver disease patients, and 1/49 (2.0%) controls [9].

Biological context of MAGEA4

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 [10].
Both the polyclonal Ab and the R5 MAb recognized a 45-kDa protein in extracts of MAGE-4 mRNA-positive lung cancers, and showed no apparent cross-reactivity with the other MAGE gene products except with MAGE-4a by immunoblot analyses and transfection experiments [4].

Anatomical context of MAGEA4

Gene MAGE-4 (HGMW-approved symbol MAGE4) is expressed in several types of tumors, but not in normal tissues, except testis and placenta [1].
New MAGE-4 antigenic peptide recognized by cytolytic T lymphocytes on HLA-A1 tumor cells [3].
Blood lymphocytes from an individual without cancer were directly labelled with these A1/MAGE-4 tetramers [3].
A24/MAGE-4 multimers were used to isolate a cytolytic T cell clone that recognized the MAGE-4 peptide from the blood cells of a donor without cancer [11].

Associations of MAGEA4 with chemical compounds

Serum MAGE-4 protein level may be useful as a marker for identification of LC-C patients suffering from HCC that is undetectable by presently available methods [9].

Other interactions of MAGEA4

Higher homology was found between MAGE-3 and -6 (98% at the nt level) and also between MAGE-4 and -41 (98%) [12].
CONCLUSIONS.: CT7, MAGEA4, and NY-ESO-1 are frequently expressed in HNMM and may be potential targets for CTA-based immunotherapy [13].
Univariate and multivariate analyses suggest that elevated serum MAGE-4 protein is more significant than AFP [2].
The aim of this study was to determine whether MAGE-4 protein is detectable in sera of patients with hepatocellular carcinoma and other liver diseases [9].

Analytical, diagnostic and therapeutic context of MAGEA4

Using PCR amplifications and digestions of the amplified product, we found that one third of the MAGE-4-positive samples expressed MAGE-4a [3].
An enzyme-linked immunosorbent assay was used to measure serum level of MAGE-4 protein [7].

References

Alternative promoters of gene MAGE4a. De Plaen, E., Naerhuyzen, B., De Smet, C., Szikora, J.P., Boon, T. Genomics (1997) [Pubmed]
Elevation of serum MAGE-4 protein levels and prediction of hepatocellular carcinogenesis in patients with liver cirrhosis. Yutani, S., Tanaka, M., Mutsumoto, H., Imai, N., Sata, M., Shichijo, S., Harada, M., Itoh, K. Jpn. J. Cancer Res. (2002) [Pubmed]
New MAGE-4 antigenic peptide recognized by cytolytic T lymphocytes on HLA-A1 tumor cells. Kobayashi, T., Lonchay, C., Colau, D., Demotte, N., Boon, T., van der Bruggen, P. Tissue Antigens (2003) [Pubmed]
Detection of MAGE-4 protein in lung cancers. Shichijo, S., Hayashi, A., Takamori, S., Tsunosue, R., Hoshino, T., Sakata, M., Kuramoto, T., Oizumi, K., Itoh, K. Int. J. Cancer (1995) [Pubmed]
Identification of MAGE-1 and MAGE-4 proteins in spermatogonia and primary spermatocytes of testis. Takahashi, K., Shichijo, S., Noguchi, M., Hirohata, M., Itoh, K. Cancer Res. (1995) [Pubmed]
The antibody 2B4 directed against the Epstein-Barr virus (EBV)-encoded nuclear antigen 1 (EBNA1) detects MAGE-4: implications for studies on the EBV association of human cancers. Hennard, C., Pfuhl, T., Buettner, M., Becker, K.F., Knöfel, T., Middeldorp, J., Kremmer, E., Niedobitek, G., Grässer, F. J. Pathol. (2006) [Pubmed]
Detection of MAGE-4 protein in sera of patients with head-and-neck squamous-cell carcinoma. Iwamoto, O., Nagao, Y., Shichijo, S., Eura, M., Kameyama, T., Itoh, K. Int. J. Cancer (1997) [Pubmed]
Expression of MAGE genes in primary and metastatic cutaneous melanoma. Brasseur, F., Rimoldi, D., Liénard, D., Lethé, B., Carrel, S., Arienti, F., Suter, L., Vanwijck, R., Bourlond, A., Humblet, Y. Int. J. Cancer (1995) [Pubmed]
Detection of MAGE-4 protein in the sera of patients with hepatitis-C virus-associated hepatocellular carcinoma and liver cirrhosis. Tsuzurahara, S., Sata, M., Iwamoto, O., Shichijo, S., Kojiro, M., Tanikawa, K., Itoh, K. Jpn. J. Cancer Res. (1997) [Pubmed]
Cloning and analysis of MAGE-1-related genes. Ding, M., Beck, R.J., Keller, C.J., Fenton, R.G. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
A new MAGE-4 antigenic peptide recognized by cytolytic T lymphocytes on HLA-A24 carcinoma cells. Ottaviani, S., Colau, D., van der Bruggen, P., der Bruggen, P. Cancer Immunol. Immunother. (2006) [Pubmed]
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]
Expression and significance of cancer testis antigens in primary mucosal melanoma of the head and neck. Prasad, M.L., Jungbluth, A.A., Patel, S.G., Iversen, K., Hoshaw-Woodard, S., Busam, K.J. Head & neck. (2004) [Pubmed]

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MAGEA4	Macaca mulatta
LOC465910	Pan troglodytes

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