Histone deacetylase inhibition and estrogen signalling in human breast cancer cells

Biochem Pharmacol. 2004 Sep 15;68(6):1239-46. doi: 10.1016/j.bcp.2004.04.031.


Estrogens are steroid hormones, which act through specific nuclear estrogen receptors (ERalpha and ERbeta) and are important regulators of breast cancer growth. These receptors control gene expression by recruiting transcriptional cofactors that exhibit various enzymatic activities such as histone acetyltransferase or histone deacetylase (HDAC) which target histone as well as non-histone substrates. The ERalpha itself and some of the transcriptional regulators have been shown to be acetylated proteins. Research performed over the last decade has highlighted the role of HDAC inhibitors (HDACi) as modulators of transcriptional activity and as a new class of therapeutic agents. In human cancer cells, inhibition of HDACs controls the expression of the ERalpha gene and the transcriptional activity in response to partial antiestrogens such as 4-hydroxytamoxifen. Various HDACi strongly inhibit breast cancer cell proliferation and ERalpha-negative (ER-) appear less sensitive than ERalpha-positive (ER+) cell lines. p21WAF1/CIP1 gene expression, in relation with ERalpha levels, could play a role in this differential response of breast cancer cells to hyperacetylating agents.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetylation / drug effects
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Enzyme Inhibitors / pharmacology*
  • Estrogen Receptor Modulators / pharmacology
  • Estrogen Receptor alpha
  • Estrogens / physiology*
  • Gene Expression Regulation / drug effects
  • Histone Deacetylase Inhibitors*
  • Humans
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism*
  • Signal Transduction / physiology
  • Tumor Cells, Cultured


  • Enzyme Inhibitors
  • Estrogen Receptor Modulators
  • Estrogen Receptor alpha
  • Estrogens
  • Histone Deacetylase Inhibitors
  • Receptors, Estrogen