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


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.


CONCLUSIONS
The ERbeta promoter is differentially methylated in ovarian cancer cells. Moreover, AzaC and TSA can inhibit ovarian cancer cell growth.
Yap
Oi Wah Stephanie
OW
Department of Obstetrics and Gynecology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Bhat
Ganapathy
G
Liu
Liang
L
Tollefsbol
Trygve O
TO