去甲基化剂5-氮杂-2'-脱氧胞苷对淋巴样细胞中MAGE基因的诱导作用。
Induction of MAGE genes in lymphoid cells by the demethylating agent 5-aza-2'-deoxycytidine.
作者信息
Shichijo S, Yamada A, Sagawa K, Iwamoto O, Sakata M, Nagai K, Itoh K
机构信息
Department of Immunology, Kurume University School of Medicine, Fukuoka.
出版信息
Jpn J Cancer Res. 1996 Jul;87(7):751-6. doi: 10.1111/j.1349-7006.1996.tb00288.x.
Abstract
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.
摘要
编码可被细胞毒性T淋巴细胞识别的肿瘤抗原的MAGE基因是癌症特异性免疫治疗的合适靶分子。我们研究了去甲基化剂5-氮杂-2'-脱氧胞苷（DAC）是否能在正常和恶性淋巴细胞中诱导MAGE-1、-2、-3和-6基因的表达。在大多数情况下，DAC在来自健康供体的PHA/白细胞介素-2（IL-2）激活的T细胞以及MAGE阴性的T和B细胞白血病中均能诱导这些MAGE基因。它还能在IL-2依赖的T细胞克隆中诱导MAGE-1基因表达，并能在爱泼斯坦-巴尔病毒转化的B细胞系中诱导所有检测的MAGE基因。用抗MAGE-1多克隆抗体进行蛋白质印迹分析证实了细胞中MAGE-1蛋白的表达。因此，去甲基化是在正常和恶性淋巴细胞中诱导MAGE基因的有效刺激因素。
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