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


RESULTS
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.


CONCLUSIONS
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.
Menendez
Laura
L
Department of Genetics, University of Georgia, Athens, GA 30605, USA. lmenen@uga.edu
Walker
L DeEtte
LD
Matyunina
Lilya V
LV
Totten
Kimberly A
KA
Benigno
Benedict B
BB
McDonald
John F
JF
D000328:Adult; D000368:Aged; D001374:Azacitidine / Q000494:pharmacology; D001483:Base Sequence; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006680:HLA Antigens / Q000235:genetics*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D024363:Transcription Initiation Site
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D001374:Azacitidine