Induction of MAGE genes in lymphoid cells by the demethylating agent 5-aza-2'-deoxycytidine.
MAGE genes encoding tumor antigens recognized by cytotoxic T lymphocytes are appropriate target molecules for specific immunotherapy of cancer. We have investigated whether the demethylating agent 5-aza-2'-deoxycytidine (DAC) induces MAGE-1, -2, -3, and -6 in normal and malignant lymphoid cells. DAC induced these MAGE genes in both PHA/interleukin-2 (IL-2)-activated T cells from healthy donors and MAGE-negative T and B cell leukemias in most cases. It also induced MAGE-1 in IL-2-dependent T cell clones and all MAGE genes tested in Epstein-Barr virus-transformed B cell lines. Expression of MAGE-1 protein in the cells was confirmed by western blot analysis with anti-MAGE-1 polyclonal antibody. Therefore, demethylation is a potent stimulus to induce MAGE genes in both normal and malignant lymphoid cells.
Shichijo
S
S
Department of Immunology, Kurume University School of Medicine, Fukuoka.
Yamada
A
A
Sagawa
K
K
Iwamoto
O
O
Sakata
M
M
Nagai
K
K
Itoh
K
K
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001483:Base Sequence; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors*; D003640:Dealkylation; D000077209:Decitabine; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000378:metabolism; D058950:Melanoma-Specific Antigens; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*
D000951:Antigens, Neoplasm; D004791:Enzyme Inhibitors; D007376:Interleukin-2; C072011:MAGEA1 protein, human; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine