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. MAGE-1, -2, -3/-6 and -4 genes were expressed, respectively, at the mRNA level in 6, 7, 20 and 7 of 53 lung cancers (50 non-small-cell lung cancers and 3 small-cell lung cancers) by the reverse transcription-polymerase chain reaction (RT-PCR) method. Polyclonal antibody (Ab) and monoclonal antibody (MAb) against recombinant MAGE-4b protein were developed to detect MAGE-4 protein. 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. MAGE-4 protein was detected on 13 of 44 (30%) lung cancers (18 to 55,989 pg/mg) by ELISA with the polyclonal Ab and R5 MAb. These 13 lung cancers consisted of 6 of 6 MAGE-4 mRNA-detectable and 7 of 38 MAGE-4 mRNA-undetectable lung cancers. Histologically, these comprised 7 of 10 squamous-cell carcinomas, 4 of 30 adenocarcinomas and 2 of 3 small-cell lung cancers. The proportions of MAGE gene-positive samples, at both the mRNA and protein levels, correlated with the size of the primary tumors and with regional node involvement. These results should provide important information on specific immunotherapy of lung cancers using MAGE gene products.
The MAGE gene family, encoding tumor-rejection antigens recognized by cytotoxic T lymphocytes, is frequently expressed in human solid cancers. However, its expression in leukemia has not been well studied. We have investigated MAGE gene expression at the mRNA level in human leukemia. The MAGE gene family was expressed in 17 of 34 (50%) examples of T cell leukemia (12/21 patients' peripheral blood mononuclear cells and 5/13 cell lines), in 7 of 16 (44%) cases of B cell leukemia (1/8 and 6/8 respectively), but in none of 23 myelomonocytic leukemia cases (0/16 and 0/7), as evaluated by the primers common to the MAGE-1, -3, -4 (-4a and/or -4b), and -6 genes and the semi-quantificative reverse transcription/polymerase chain reaction method. None of a panel of normal lymphoid cells expressed the MAGE gene family. As revealed by the primers specific for each of the MAGE genes, the MAGE-1, -2, -3, -4 or -6 gene was expressed in 8, 8, 6, 2, or 6 respectively out of 23 types of leukemia cell lines. Expression of the MAGE-1 protein in both the cell lines and patients' cells was confirmed by immunoblot analysis with the polyclonal antibody to recombinant MAGE-1 protein. Cellular MAGE-4 protein in the cell lines was measured by an enzyme-linked immunosorbent assay with the polyclonal and monoclonal antibodies to recombinant MAGE-4b protein. In summary, the MAGE gene family was found to be expressed in the substantial proportion of T cell leukemias, but in no case of myelomonocytic leukemia. Antigens coded by the MAGE gene family could be important molecules for understanding specific immunity against lymphocytic leukemia.
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