Epigenetic changes within the promoter region of the HLA-G gene in ovarian tumors

• Published in: Molecular cancer Vol. 7; no. 1; p. 43
• Main Authors: Menendez, Laura, Walker, L DeEtte, Matyunina, Lilya V, Totten, Kimberly A, Benigno, Benedict B, McDonald, John F
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 22-05-2008; BioMed Central; BMC
• Subjects: Adult; Aged; Azacitidine - pharmacology; Base Sequence; Cell Line, Tumor; Control; CpG Islands - genetics; DNA Methylation - drug effects; Epigenesis, Genetic - drug effects; Epigenetic inheritance; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelial Cells - pathology; Female; Gene Expression Regulation, Neoplastic - drug effects; Genetic aspects; Histocompatibility antigens; Histocompatibility Antigens Class I - genetics; HLA Antigens - genetics; HLA histocompatibility antigens; HLA-G Antigens; Humans; Identification and classification; Middle Aged; Ovarian cancer; Ovarian Neoplasms - genetics; Promoter Regions, Genetic - genetics; Reverse Transcriptase Polymerase Chain Reaction; Risk factors; Transcription Initiation Site; United States
• ISSN: 1476-4598; 1476-4598
• DOI: 10.1186/1476-4598-7-43

Previous findings have suggested that epigenetic-mediated HLA-G expression in tumor cells may be associated with resistance to host immunosurveillance. To explore the potential role of DNA methylation on HLA-G expression in ovarian cancer, we correlated differences in HLA-G expression with methylation changes within the HLA-G regulatory region in an ovarian cancer cell line treated with 5-aza-deoxycytidine (5-aza-dC) and in malignant and benign ovarian tumor samples and ovarian surface epithelial cells (OSE) isolated from patients with normal ovaries.
A region containing an intact hypoxia response element (HRE) remained completely methylated in the cell line after treatment with 5-aza-dC and was completely methylated in all of the ovarian tumor (malignant and benign) samples examined, but only variably methylated in normal OSE samples. HLA-G expression was significantly increased in the 5-aza-dC treated cell line but no significant difference was detected between the tumor and OSE samples examined.
Since HRE is the binding site of a known repressor of HLA-G expression (HIF-1), we hypothesize that methylation of the region surrounding the HRE may help maintain the potential for expression of HLA-G in ovarian tumors. The fact that no correlation exists between methylation and HLA-G gene expression between ovarian tumor samples and OSE, suggests that changes in methylation may be necessary but not sufficient for HLA-G expression in ovarian cancer.