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Inhibition of DNMT1 with 5‐aza‐2′‐deoxycytidine induces expression of tumor antigens (GAGE, MAGE, PAGE, and CT45) in MCF7 cells
Author(s) -
Lobo Rebecca C.,
Lee KyungSeon,
Green Ralph,
Miller Joshua W.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.925.4
Subject(s) - antigen , microbiology and biotechnology , tumor antigen , cancer research , biology , dna methylation , cancer cell , dnmt1 , epigenetics , gene expression , cancer , chemistry , gene , immune system , immunotherapy , immunology , genetics
Cancer cells often express tumor antigens that are recognized by host cytolytic T lymphocytes. Such antigens include GAGE (G antigen), MAGE (melanoma specific antigen), PAGE (prostate specific antigen), and CT45 (cancer/testis antigen). Repression of tumor antigens is a mechanism by which cancer cells may evade recognition by the immune system. Methylation of CpG sites in promoter regions of specific genes leads to recruitment of methylated DNA binding proteins and co‐repressors that cause chromatin compaction and gene repression. This is a key mechanism contributing to abnormal gene expression patterns observed in cancer cells. We are investigating the effect on gene expression of 5‐aza‐2′‐deoxycytidine (ADC), an inhibitor of DNA methyltransferase 1 (DNMT1), in the human breast cancer cell line, MCF7. Cells were treated in vitro for 72 hours with 1 µM ADC in DMSO. RNA was then isolated for microarray analysis (Affymetrix). Compared with cells treated with DMSO alone, ADC‐treated cells exhibited increased expression (≥2‐fold) of 38 genes. Ten of these genes were members of the GAGE, MAGE, PAGE, or CT45 families, with all 10 exhibiting >5‐fold increased expression. These results suggest that tumor antigens are repressed epigenetically in MCF7 cells. De‐repression of these antigens using drugs that target epigenetic factors may provide an effective strategy for cancer treatment. American Cancer Society