The SMAGE gene family is expressed in post-meiotic spermatids during mouse germ cell differentiation

Chomez, Patrick; Williams, Richard C.; Backer, Olivier De; Boon, Thierry; Vennström, Björn

doi:10.1007/bf00186613

Cited by 29 publications

(14 citation statements)

References 13 publications

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“…Like these genes, LAGE-1 is not expressed at a significant level in normal adult tissues with the exception of testis. The cells that express MAGE genes in testis appear to be the germ line cells (Chomez et al, 1995;Takahashi et al, 1995), and we consider it likely that germ line cells are also those that express LAGE-1. The types of tumors, such as melanomas, head and neck, lung and bladder cancers, where LAGE-1 expression is often observed are also those that express MAGE genes.…”

Section: Discussionmentioning

confidence: 99%

LAGE-1, a new gene with tumor specificity

et al. 1998

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Representational difference analysis was used to identify genes that are expressed in a human melanoma cell line and not in normal skin. A cDNA clone that appeared to be specific for tumors was obtained and the corresponding gene was sequenced. This new gene was named LAGE‐1. Using a LAGE‐1 probe to screen a cDNA library from the same melanoma cell line, we identified a closely related gene, which proved to be identical to NY‐ESO‐1, a gene recently reported to code for an antigen recognized by autologous antibodies in an esophageal squamous cell carcinoma. Gene LAGE‐1 maps to Xq28. It comprises 3 exons. Alternative splicing produces 2 major transcripts encoding polypeptides of 210 and 180 residues, respectively. Expression of LAGE‐1 was observed in 25–50% of tumor samples of melanomas, non‐small‐cell lung carcinomas, bladder, prostate and head and neck cancers. The only normal tissue that expressed the gene was testis. As for MAGE‐A1, expression of LAGE‐1 is induced by deoxy‐azacytidine in lymphoblastoid cells, suggesting that tumoral expression is due to demethylation. The expression of LAGE‐1 is strongly correlated with that of NY‐ESO‐1. It is also clearly correlated with the expression of MAGE genes. Int. J. Cancer 76:903–908, 1998.© 1998 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

LAGE-1, a new gene with tumor specificity

et al. 1998

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“…MAGE-D has also been mapped to the same region (28). All MAGE superfamily proteins are encoded on a single large exon, except for MAGE-D (18,28) and the presently described magphinins, in which the respective coding regions are separated into many exons. Remarkably, the intron/exon boundaries of the magphinin-encoding region, particularly in the region encoding the conserved polypeptide sequences in other MAGE superfamily proteins (Fig.…”

Section: Magphinins As Novel Members Of the Mage Protein Superfamily-mentioning

confidence: 99%

“…However, common features of other MAGE superfamily proteins are that they are expressed specifically in tumor cells derived from various tissues and in the testis (12). In particular, the MAGE proteins are found in both the nucleus and cytoplasm of male germ cells (8,18). In mice, the Mage-a and -b genes are expressed in the testis as well as in blastocyst stage embryos (12,19).…”

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The Trophinin Gene Encodes a Novel Group of MAGE Proteins, Magphinins, and Regulates Cell Proliferation during Gametogenesis in the Mouse

Saburi

Nadano

Akama

et al. 2001

Journal of Biological Chemistry

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Trophinin is a membrane protein that mediates apical cell adhesion between trophoblastic cells and luminal epithelial cells of the endometrium and is implicated in the initial attachment during the process of human embryo implantation. The present study identified novel trophinin gene transcripts, which encode proteins structurally distinct from trophinin protein in the mouse. We designated these proteins "magphinins," because they share consensus amino acid sequences with MAGE (melanoma-associated antigen) superfamily proteins. Among many MAGE proteins, magphinins are closely related to NRAGE, which mediates p75 neurotrophin receptor-dependent apoptosis, and necdin, which is a strong suppressor of cell proliferation in post-mitotic neurons. There are three major forms of magphinins, i.e. magphinin-␣, -␤, and -␥, in the mouse, which are formed due to alternative usage of different exons. Northern blot analysis revealed that magphinins are expressed in brain, ovary, testis, and epididymis. In addition, Western blot analysis and in vitro translation experiments showed that magphinins expressed in the mouse ovary and testis are translation products utilizing the second initiation AUG codon and contain an active nuclear localization signal. Ectopic expression of magphinins in mammalian cells resulted in nuclear localization of magphinin and suppressed cell proliferation. Immunohistochemistry of the mouse ovary and testis showed that magphinin proteins are distributed in the cytoplasm of the male and female germ cells, whereas these proteins are translocated to the nucleus at a specific stage of gametogenesis. These results strongly suggest that magphinins regulate cell proliferation during gametogenesis in the mouse.Mammals retain distinctions with regard to the strategies used to protect and nourish their offspring during development, namely by the process of embryo implantation and placentation. The process of implantation varies markedly between species (1), and genes involved in this process display remarkably high spontaneous mutational rates (2), suggesting a strong adaptive selection pressure. The study of human embryo implantation at the molecular level is hampered by the fact that in vivo studies with an implanting embryo in place are difficult to perform and are generally considered ethically unacceptable. To overcome this problem, we established an in vitro cell culture system using two human cell lines, trophoblastic teratocarcinoma HT-H and endometrial adenocarcinoma SNG-M. These two cell types adhered with each other at their respective apical cell membranes and exhibited morphologies resembling the cells at the initial adhesion steps of embryo implantation (3, 4).Using this model system, we identified a unique protein, trophinin, by means of expression cloning. Thus a mammalian expression cDNA library constructed from HT-H cells was transfected into COS cells, and COS cells that became adhesive to SNG-M cells were selected. When COS cells acquired trophinin and trophinin-associated cytoplasmic protein...

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“…These genes are silent in normal tissues except in testis and, for some, in placenta (6,10). Recent data indicate that the expression of the MAGE genes in testis is restricted to the germ-line cells (11,12). Because male germ-line cells lack expression of the major histocompatibility complex molecules (13), they are not expected to present MAGE-encoded antigens.…”

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The activation of human gene MAGE-1 in tumor cells is correlated with genome-wide demethylation.

Smet

Backer

Faraoni

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

469

301

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Human gene MAGE-1 encodes tumorspecific antigens that are recognized on melanoma cells by autologous cytolytic T lymphocytes. This gene is expressed in a significant proportion of tumors of various histological types, but not in normal tissues except male germ-line cells. We reported previously that reporter genes driven by the MAGE-1 promoter are active not only in the tumor cell lines that express MAGE-1 but also in those that do not. This suggests that the critical factor causing the activation of MAGE-1 in certain tumors is not the presence of the appropriate transcription factors. The two major MAGE-1 promoter elements have an Ets binding site, which contains a CpG dinucleotide. We report here that these CpG are demethylated in the tumor cell lines that express MAGE-1, and are methylated in those that do not express the gene. Methylation of these CpG inhibits the binding of transcription factors, as seen by mobility shift assay. Treatment with the demethylating agent 5-aza-2'-deoxycytidine activated gene MAGE-1 not only in tumor cell lines but also in primary fibroblasts. Finally, the overall level of CpG methylation was evaluated in 20 different tumor cell lines. It was inversely correlated with the expression of MAGE-I. We conclude that the activation of MAGE-1 in cancer cells is due to the demethylation of the promoter. This appears to be a consequence of a genome-wide demethylation process that occurs in many cancers and is correlated with tumor progression.

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The SMAGE gene family is expressed in post-meiotic spermatids during mouse germ cell differentiation

Cited by 29 publications

References 13 publications

LAGE-1, a new gene with tumor specificity

LAGE-1, a new gene with tumor specificity

The Trophinin Gene Encodes a Novel Group of MAGE Proteins, Magphinins, and Regulates Cell Proliferation during Gametogenesis in the Mouse

The activation of human gene MAGE-1 in tumor cells is correlated with genome-wide demethylation.

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