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

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Date
2008-05-22Author
Menendez, Laura
Walker, L. DeEtte
Matyunina, Lilya V.
Totten, Kimberly A.
Benigno, Benedict B.
McDonald, John F.
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Show full item recordAbstract
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.
Conclusion: 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.