title: BORIS/CTCFL expression is insufficient for cancer-germline antigen gene expression and DNA hypomethylation in ovarian cell lines.
abstract: Expression of the cancer-germline (CG) (or cancer-testis) antigen gene BORIS/CTCFL has been proposed to mediate activation of CG antigen genes in cancer. Consistent with this idea, we have observed that BORIS is frequently expressed in ovarian cancer, often in conjunction with other CG genes. Here we assessed the role of BORIS in CG antigen gene regulation and DNA methylation using normal and cancerous ovarian cell lines, and the CG genes MAGE-A1, NY-ESO-1, and XAGE-1 as models. Adenoviral vectored BORIS was expressed at robust levels and exhibited predominant nuclear localization in ovarian cells. However, BORIS expression in immortalized ovarian surface epithelial cells or ovarian cancer cell lines did not induce CG antigen gene expression or lead to CG antigen promoter DNA hypomethylation. BORIS overexpression also did not alter global DNA methylation, as assessed by genomic 5-methyl-deoxycytidine levels and LINE-1 methylation. We used decitabine to further assess the role of BORIS in CG gene activation and found that decitabine treatment induced BORIS and other CG genes with similar kinetics, suggesting that BORIS induction does not account for the induction of other CG genes by decitabine in ovarian cancer cells. In agreement, siRNA knockdown of BORIS did not block decitabine-mediated induction of CG genes or DNA hypomethylation in ovarian cancer cells treated with this agent. We conclude that BORIS is insufficient for CG antigen gene expression and DNA hypomethylation in ovarian cell lines, and that additional factors are likely required for CG antigen expression in ovarian cancer.
authors.affiliation: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Woloszynska-Read
authors.forename: Smitha R
authors.initials: SR
authors.lastname: James
authors.forename: Chajoun
authors.initials: C
authors.lastname: Song
authors.forename: Boquan
authors.initials: B
authors.lastname: Jin
authors.forename: Kunle
authors.initials: K
authors.lastname: Odunsi
authors.forename: Adam R
authors.initials: AR
authors.lastname: Karpf
mesh_terms: D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D000077209:Decitabine; D044127:Epigenesis, Genetic; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009928:Organ Specificity; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000276:immunology*; D011401:Promoter Regions, Genetic; D024363:Transcription Initiation Site
chemical_list: D000951:Antigens, Neoplasm; C456540:CTCFL protein, human; D004268:DNA-Binding Proteins; D000077209:Decitabine; D001374:Azacitidine