Transcriptional activation of estrogen receptor α in human breast cancer cells by histone deacetylase inhibition

Xiaowei Yang, Anne T. Ferguson, Sharyl J. Nass, Dawn L. Phillips, Kim A. Butash, San Ming Wang, James G. Herman, Nancy E. Davidson

Research output: Contribution to journalArticle

Abstract

Recent findings have established a connection between DNA methylation and transcriptionally inactive chromatin characterized by deacetylated histones. Because the absence of estrogen receptor α (ERα) gene expression has been associated with aberrant methylation of its CpG island in a significant fraction of breast cancers, we tested whether histone deacetylase activity contributes to the transcriptional inactivation of the methylated ER gene in a panel of ER-negative human breast cancer cells. Treatment of these cells with trichostatin A, a specific histone deacetylase inhibitor, led to dose- and time-dependent re-expression of ER mRNA as detected by reverse transcription-PCR without alteration in ERα CpG island methylation. Trichostatin A-induced ER re-expression was associated with increased sensitivity to DNase I at the ER locus in MDA-MB-231 cells. These data implicate inactive chromatin mediated by histone deacetylation as a critical component of ER gene silencing in human breast cancer cells. Therefore, histone deacetylation may be a potential target for therapeutic intervention in the treatment of a subset of ER-negative breast cancers.

Original languageEnglish (US)
Pages (from-to)6890-6894
Number of pages5
JournalCancer Research
Volume60
Issue number24
StatePublished - Dec 15 2000

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Yang, X., Ferguson, A. T., Nass, S. J., Phillips, D. L., Butash, K. A., Wang, S. M., Herman, J. G., & Davidson, N. E. (2000). Transcriptional activation of estrogen receptor α in human breast cancer cells by histone deacetylase inhibition. Cancer Research, 60(24), 6890-6894.