Title:
Epigenetic changes within the promoter region of the HLA-G gene in ovarian tumors
Epigenetic changes within the promoter region of the HLA-G gene in ovarian tumors
Author(s)
Menendez, Laura
Walker, L. DeEtte
Matyunina, Lilya V.
Totten, Kimberly A.
Benigno, Benedict B.
McDonald, John F.
Walker, L. DeEtte
Matyunina, Lilya V.
Totten, Kimberly A.
Benigno, Benedict B.
McDonald, John F.
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Abstract
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.
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Date Issued
2008-05-22
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