Histone deacetylase 6 regulates estrogen receptor alpha in uterine leiomyoma

Reprod Sci. 2011 Aug;18(8):755-62. doi: 10.1177/1933719111398147. Epub 2011 Mar 18.

Abstract

Histone deacetylase 6 (HDAC) 6 is a regulatory factor in the endocrine traffic network that controls growth factor receptor stability. Histone deacetylase 6 expression and its pathogenic role in the uterine leiomyoma have not been studied. Here, we demonstrated that there was a consistent pattern of increasing HDAC6 and estrogen receptor (ER) α expression in leiomyoma samples. For all individual cases, expression of HDAC6 in the normal myometrium or leiomyoma positively correlated with ERα expression. The spearman's rho (ρ) was .53 (P = .008) between HDAC6 and ERα in normal myometrium and, more significantly, the spearman rho was .80 (P < .001) between HDAC6 and ERα in leiomyoma. In ELT-3 leiomyoma cells, silencing HDAC6 expression substantially reduced ERα expression, lowered estrogen response, and inhibited ELT-3 cell growth. Our results, taken together, are the first to provide experimental evidence suggesting that HDAC6 may be an essential molecular therapeutic target in controlling leiomyoma growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Line
  • Cell Proliferation / drug effects
  • Estrogen Receptor alpha / metabolism*
  • Female
  • Histone Deacetylase 6
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Humans
  • Immunohistochemistry
  • Leiomyoma / enzymology
  • Leiomyoma / metabolism*
  • Middle Aged
  • Neoplasms, Hormone-Dependent / metabolism*
  • RNA / chemistry
  • RNA / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Uterine Neoplasms / enzymology
  • Uterine Neoplasms / metabolism*

Substances

  • Estrogen Receptor alpha
  • estrogen receptor alpha, human
  • RNA
  • HDAC6 protein, human
  • Histone Deacetylase 6
  • Histone Deacetylases