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. 2009 Jan;29(1):139-44.

Epigenetic modifications of the Estrogen receptor beta gene in epithelial ovarian cancer cells

Oi Wah Stephanie Yap  1 , Ganapathy Bhat, Liang Liu, Trygve O Tollefsbol
Affiliations

Epigenetic modifications of the Estrogen receptor beta gene in epithelial ovarian cancer cells

Oi Wah Stephanie Yap et al. Anticancer Res. 2009 Jan.

Abstract

Background: The mechanisms of estrogen insensitivity or estrogen resistance in ovarian cancer cells are not known. Studies on regulation of the estrogen receptor (ER) gene have suggested a role for epigenetics in silencing ER expression.

Materials and methods: Cells from insensitive ovarian cancer cells, SKOV3 and HEY, were cultured with and without the DNA methyltransferase (DNMT) inhibitor, 5-aza-2'-deoxycytidine (AzaC) and the histone deacetylase (HDAC) inhibitor, trichostatin (TSA). ERbeta promoter methylation was examined using bisulfite sequencing. RNA was collected for oligonucleotide array studies.

Results: Cell type-specific ERbeta promoter methylation was found as well as relative hypomethylation of the ERbeta promoter in SKOV3 compared to HEY cells. Preferential demethylation of specific CpGs by different treatments was found. AzaC and TSA resulted in significant tumor growth inhibition and alterations in expression of numerous genes.

Conclusion: The ERbeta promoter is differentially methylated in ovarian cancer cells. Moreover, AzaC and TSA can inhibit ovarian cancer cell growth.

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Figures

Figure 1
Figure 1
Effect of AzaC, TSA, and AzaC + TSA on SKOV3 (A, C, E) and HEY (B, D, F) cell proliferation. Cell counts were made daily for cells treated with AzaC and the combination of AzaC + TSA, and at 12, 18, 24, and 48 hours after treatment with TSA using a Coulter counter. Shown is the average (n=3) for each time point and treatment condition; bars, SEM; *p<0.05 determined by Student’s t-test.
Figure 2
Figure 2
Real-time PCR quantification of ERβ mRNA expression following treatments with AzaC, TSA, and AzaC + TSA in SKOV3 (A) and HEY (B) cells. All measurements were normalized to 18S rRNA expression. Graphs are the average ± SEM of three experiments.
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