Roles of Histone Deacetylase and DNA Methylation in Estrogen Receptor alpha Expression in Breast Cancer

摘要

The proposal tests the hypothesis that histone deacetylase activity contributes to the transcriptional repression of the methylated estrogen receptor alpha (ER) gene. It further postulates that inhibition of histone deacetylase (HDAC) and DNA methylation may act together to reactivate the ER gene. Studies to date show that the HDAC inhibitor trichostatin A, can reactivate ER expression in ER-negative breast cancer cell line. Combined treatment with HDAC inhibitors and demethylating agents can synergistically reactivate expression of ER-negative breast cancer cell lines.